NO-independent, haem-dependent soluble guanylate cyclase stimulators

Handbook of Experimental Pharmacology

Volumn 191, Issue , 2009, Pages 277-308

  Stasch, Johannes Peter ^a   Hobbs, Adrian J ^b  

^a BAYER PHARMA AG   (Germany)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

1 BENZYL 3 (5 HYDROXYMETHYL 2 FURYL)INDAZOLE; 15 HYDROXY 11ALPHA,9ALPHA EPOXYMETHANOPROSTA 5,13 DIENOIC ACID; 2 [1 (2 FLUOROBENZYL) 1H PYRAZOLO[3,4 B]PYRIDIN 3 YL] 5 MORPHOLINO 4,6 PYRIMIDINEDIAMINE; 3 [2 (4 CHLOROPHENYLTHIO)PHENYL] N (4 DIMETHYLAMINOBUTYL)ACRYLAMIDE; 4 [[4 CARBOXYBUTYL[2 [(4 PHENETHYLBENZYL)OXY]PHENETHYL]AMINO]METHYL]BENZOIC ACID; 4 AMINO 5 CYCLOPROPYL 2 [1 (2 FLUOROBENZYL) 1H PYRAZOLO[3,4 B]PYRIDIN 3 YL]PYRIMIDINE; A 344905; A 778935; BAY 63 2521; CFM 1571; GUANYLATE CYCLASE ACTIVATOR; INDAZOLE DERIVATIVE; N(G) NITROARGININE METHYL ESTER; NITRIC OXIDE; SILDENAFIL; UNCLASSIFIED DRUG; VASODILATOR AGENT; ACRYLAMIDE DERIVATIVE; BAY 63-2521; CELL RECEPTOR; ENZYME ACTIVATOR; GUANYLATE CYCLASE; HEME; PYRIMIDINE DERIVATIVE; SOLUBLE GUANYLYL CYCLASE;

ATHEROSCLEROSIS; CARDIOVASCULAR DISEASE; CLINICAL TRIAL; DRUG ACTIVITY; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENTIATION; ERECTILE DYSFUNCTION; HEART FAILURE; HUMAN; HYPERTENSION; KIDNEY FAILURE; KIDNEY FIBROSIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN PROCESSING; PULMONARY HYPERTENSION; RESTENOSIS; REVIEW; SIGNAL TRANSDUCTION; SMOOTH MUSCLE RELAXATION; THROMBOSIS; TREATMENT INDICATION; VASODILATATION; ANIMAL; DRUG EFFECT; METABOLISM; PATHOPHYSIOLOGY;

ACRYLAMIDES; ANIMALS; CARDIOVASCULAR DISEASES; CLINICAL TRIALS AS TOPIC; ENZYME ACTIVATORS; GUANYLATE CYCLASE; HEME; HUMANS; INDAZOLES; NITRIC OXIDE; PYRIMIDINES; RECEPTORS, CYTOPLASMIC AND NUCLEAR; SIGNAL TRANSDUCTION;

EID: 61749096117     PISSN: 01712004     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-3-540-68964-5_13     Document Type: Review

References (233)

1. Ahluwalia A, Foster P, Scotland RS, McLean PG, Mathur A, Perretti M, Moncada S, Hobbs AJ (2004) Antiinflammatory activity of soluble guanylate cyclase: cGMP-dependent downregulation of P-selectin expression and leukocyte recruitment. Proc Natl Acad Sci USA 101:1386-1391
2. Aliyu ZY, Kato GJ, Taylor JT, Babadoko A, Mamman AI, Gordeuk VR, Gladwin MT (2008) Sickle cell disease and pulmonary hypertension in Africa: A global perspective and review of epidemiology, pathophysiology, and management. Am J Hematol 83:63-70
3. Amirmansour C, Vallance P, Bogle RG (1999) Tyrosine nitration in blood vessels occurs with increasing nitric oxide concentration. Br J Pharmacol 127:788-794
4. Andersson KE (2001) Pharmacology of penile erection. Pharmacol Rev 53:417-450
5. Atz AM, Adatia I, Wessel DL (1996) Rebound pulmonary hypertension after inhalation of nitric oxide. Ann Thorac Surg 62:1759-1764
6. Baracat JS, Teixeira CE, Okuyama CE, Priviero FB, Faro R, Antunes E, De Nucci G (2003) Relaxing effects induced by the soluble guanylyl cyclase stimulator BAY 41-2272 in human and rabbit corpus cavernosum. Eur J Pharmacol 477:163-169
7. Becker EM, Alonso-Alija C, Apeler H, Gerzer R, Minuth T, Pleiss U, Schmidt P, Schramm M, Schroder H, Schroeder W, Steinke W, Straub A, Stasch JP (2001) NO-independent regulatory site of direct sGC stimulators like YC-1 and BAY 41-2272. BMC Pharmacol 1:13
8. Becker EM, Schmidt P, Schramm M, Schroder H, Walter U, Hoenicka M, Gerzer R, Stasch JP (2000) The vasodilator-stimulated phosphoprotein (VASP): target of YC-1 and nitric oxide effects in human and rat platelets. J Cardiovasc Pharmacol 35:390-397
9. Berkan O, Bagcivan I, Kaya T, Yildirim K, Yildirim S, Dogan K (2007) Investigation of the vasorelaxant effects of 3-(5-hydroxymethyl-2'-furyl)-1- benzyl indazole (YC-1) and diethylamine/nitric oxide (DEA/NO) on the human radial artery used as coronary bypass graft. Can J Physiol Pharmacol 85:521-526
10. Bischoff E, Schramm M, Straub A, Feurer A, Stasch JP (2003) BAY 41-2272: a stimulator of soluble guanylyl cyclase induces nitric oxide-dependent penile erection in vivo. Urology 61:464-467
11. Bischoff E, Stasch JP (2004) Effects of the sGC stimulator BAY 41-2272 are not mediated by phosphodiesterase 5 inhibition. Circulation 110:320-321; author reply e320-e321
12. Bloch KD, Ichinose F, Roberts JD Jr, Zapol WM (2007) Inhaled NO as a therapeutic agent. Cardiovasc Res 75:339-348
13. Boerrigter G, Burnett JC Jr (2004) Recent advances in natriuretic peptides in congestive heart failure. Expert Opin Investig Drugs 13:643-652
14. Boerrigter G, Costello-Boerrigter LC, Cataliotti A, Tsuruda T, Harty GJ, Lapp H, Stasch JP, Burnett JC Jr (2003) Cardiorenal and humoral properties of a novel direct soluble guanylate cyclase stimulator BAY 41-2272 in experimental congestive heart failure. Circulation 107:686-689
15. Brandes RP, Kim D, Schmitz-Winnenthal FH, Amidi M, Godecke A, Mulsch A, Busse R (2000) Increased nitrovasodilator sensitivity in endothelial nitric oxide synthase knockout mice: role of soluble guanylyl cyclase. Hypertension 35:231-236
16. Bredt DS (2003) Nitric oxide signaling in brain: potentiating the gain with YC-1. Mol Pharmacol 63:1206-1208
17. Brunton TL (1867) Use of nitrite of amyl in angina patients. Lancet 2:97-98
18. Budworth J, Meillerais S, Charles I, Powell K (1999) Tissue distribution of the human soluble guanylate cyclases. Biochem Biophys Res Commun 263:696-701
19. Burney S, Caulfield JL, Niles JC, Wishnok JS, Tannenbaum SR (1999) The chemistry of DNA damage from nitric oxide and peroxynitrite. Mutat Res 424:37-49
20. Cary SP, Winger JA, Marletta MA (2005) Tonic and acute nitric oxide signaling through soluble guanylate cyclase is mediated by nonheme nitric oxide, ATP, and GTP. Proc Natl Acad Sci U S A 102:13064-13069
21. Cau SB, Dias-Junior CA, Montenegro MF, de Nucci G, Antunes E, Tanus-Santos JE (2008) Dosedependent beneficial hemodynamic effects of BAY 41-2272 in a canine model of acute pulmonary thromboembolism. Eur J Pharmacol 581:132-137
22. Cellek S (2003) The Rho-kinase inhibitor Y-27632 and the soluble guanylyl cyclase activator BAY 41-2272 relax rabbit vaginal wall and clitoral corpus cavernosum. Br J Pharmacol 138:287-290
23. Cetin A, Kaya T, Demirkoprulu N, Karadas B, Duran B, Cetin M (2004) YC-1, a nitric oxideindependent activator of soluble guanylate cyclase, inhibits the spontaneous contractions of isolated pregnant rat myometrium. J Pharmacol Sci 94:19-24
24. Chapman KR, Mannino DM, Soriano JB, Vermeire PA, Buist AS, Thun MJ, Connell C, Jemal A, Lee TA, Miravitlles M, Aldington S, Beasley R (2006) Epidemiology and costs of chronic obstructive pulmonary disease. Eur Respir J 27:188-207
25. Che Y, Ellis A, Li CG (2005) Enhanced responsiveness to nitric oxide, nitroxyl anions, and nitrergic transmitter by 3-(5-hydroxymethyl-2-furyl)-1- benzyl indazole in the rat anococcygeus muscle. Nitric Oxide 13:118-124
26. Chen Z, Zhang J, Stamler JS (2002) Identification of the enzymatic mechanism of nitroglycerin bioactivation. Proc Natl Acad Sci U S A 99:8306-8311
27. Chiang WC, Teng CM, Lin SL, Chen YM, Tsai TJ, Hsieh BS (2005) YC-1-inhibited proliferation of rat mesangial cells through suppression of cyclin D1-independent of cGMP pathway and partially reversed by p38 MAPK inhibitor. Eur J Pharmacol 517:1-10
28. Chien WL, Liang KC, Teng CM, Kuo SC, Lee FY, Fu WM (2003) Enhancement of long-term potentiation by a potent nitric oxide-guanylyl cyclase activator, 3-(5-hydroxymethyl-2-furyl)-1-benzyl-indazole. Mol Pharmacol 63:1322-1328
29. Chien WL, Liang KC, Teng CM, Kuo SC, Lee FY, Fu WM (2005) Enhancement of learning behaviour by a potent nitric oxide-guanylate cyclase activator YC-1. Eur J Neurosci 21:1679-1688
30. Chien YH, Bau DT, Jan KY (2004) Nitric oxide inhibits DNA-adduct excision in nucleotide excision repair. Free Radic Biol Med 36:1011-1017
31. Chirkov YY, Horowitz JD (2007) Impaired tissue responsiveness to organic nitrates and nitric oxide: a new therapeutic frontier? Pharmacol Ther 116:287-305
32. Chockalingam A, Gnanavelu G, Venkatesan S, Elangovan S, Jagannathan V, Subramaniam T, Alagesan R, Dorairajan S (2005) Efficacy and optimal dose of sildenafil in primary pulmonary hypertension. Int J Cardiol 99:91-95
33. Chou LC, Huang LJ, Yang JS, Lee FY, Teng CM, Kuo SC (2007) Synthesis of furopyrazole analogs of 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) as novel anti-leukemia agents. Bioorg Med Chem 15:1732-1740
34. Chun YS, Yeo EJ, Choi E, Teng CM, Bae JM, Kim MS, Park JW (2001) Inhibitory effect of YC-1 on the hypoxic induction of erythropoietin and vascular endothelial growth factor in Hep3B cells. Biochem Pharmacol 61:947-954
35. D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Kernis JT, et al (1991) Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 115:343-349Demirkoprulu N, Cetin M, Bagcivan I, Kaya T, Soydan AS, Karadas B, Cetin A (2005) Comparative relaxant effects of YC-1 and DETA/NO on spontaneous contractions and the levels of cGMP of isolated pregnant rat myometrium. Eur J Pharmacol 517:240-245
36. Dempsey OJ, Kerr KM, Gomersall L, Remmen H, Currie GP (2006) Idiopathic pulmonary fibrosis: an update. QJM 99:643-654
37. Demirkoprulu N, Cetin M, Bagcivan I, Kaya T, Soydan AS, Karadas B, Cetin A (2005) Comparative relaxant effects of YC-1 and DETA/NO on spontaneous contractions and the levels of cGMP of isolated pregnant rat myometrium. Eur J Pharmacol 517:240-245
38. Dempsey OJ, Kerr KM, Gomersall L, Remmen H, Currie GP (2006) Idiopathic pulmonary fibrosis:an update. QJM 99:643-654
39. Denninger JW, Schelvis JP, Brandish PE, Zhao Y, Babcock GT, Marletta MA (2000) Interaction of soluble guanylate cyclase with YC-1: kinetic and resonance Raman studies. Biochemistry 39:4191-4198
40. Denton CP, Nihtyanova SI (2007) Therapy of pulmonary arterial hypertension in systemic sclerosis: an update. Curr Rheumatol Rep 9:158-164
41. Derbyshire ER, Marletta MA (2007) Butyl isocyanide as a probe of the activation mechanism of soluble guanylate cyclase: investigating the role of non-heme nitric oxide. J Biol Chem 282:35741-35748
42. Derbyshire ER, Gunn A, Ibrahim M, Spiro TG, Britt RD, Marletta MA (2008) Characterization of two different five-coordinate soluble guanylate cyclase ferrous-nitrosyl complexes. Biochemistry 47:3892-3899
43. Deruelle P, Balasubramaniam V, Kunig AM, Seedorf GJ, Markham NE, Abman SH (2006) BAY 41-2272, a direct activator of soluble guanylate cyclase, reduces right ventricular hypertrophy and prevents pulmonary vascular remodeling during chronic hypoxia in neonatal rats. Biol Neonate 90:135-144
44. Deruelle P, Grover TR, Abman SH (2005a) Pulmonary vascular effects of nitric oxide-cGMP augmentation in a model of chronic pulmonary hypertension in fetal and neonatal sheep. Am J Physiol Lung Cell Mol Physiol 289:L798-L806
45. Deruelle P, Grover TR, Storme L, Abman SH (2005b) Effects of BAY 41-2272, a soluble guanylate cyclase activator, on pulmonary vascular reactivity in the ovine fetus. Am J Physiol Lung Cell Mol Physiol 288:L727-L733
46. Dumitrascu R, Weissmann N, Ghofrani HA, Dony E, Beuerlein K, Schmidt H, Stasch JP, Gnoth MJ, Seeger W, Grimminger F, Schermuly RT (2006) Activation of soluble guanylate cyclase reverses experimental pulmonary hypertension and vascular remodeling. Circulation 113: 286-295
47. Dunkern TR, Feurstein D, Rossi GA, Sabatini F, Hatzelmann A (2007) Inhibition of TGF-beta induced lung fibroblast to myofibroblast conversion by phosphodiesterase inhibiting drugs and activators of soluble guanylyl cyclase. Eur J Pharmacol 572:12-22
48. Erusalimsky JD, Moncada S (2007) Nitric oxide and mitochondrial signaling: from physiology to pathophysiology. Arterioscler Thromb Vasc Biol 27:2524-2531
49. Evgenov OV, Ichinose F, Evgenov NV, Gnoth MJ, Falkowski GE, Chang Y, Bloch KD, Zapol WM (2004) Soluble guanylate cyclase activator reverses acute pulmonary hypertension and augments the pulmonary vasodilator response to inhaled nitric oxide in awake lambs. Circulation 110:2253-2259
50. Evgenov OV, Kohane DS, Bloch KD, Stasch JP, Volpato GP, Bellas E, Evgenov NV, Buys ES, Gnoth MJ, Graveline AR, Liu R, Hess DR, Langer R, Zapol WM (2007) Inhaled agonists of soluble guanylate cyclase induce selective pulmonary vasodilation. Am J Respir Crit Care Med 176:1-8
51. Evgenov OV, Egorina EM, Stasch JP, Sovershaev MA. Inhibition of expression and procoagulant activity of tissue factor by soluble guanylate cyclase agonists in monocytes and endothelial cells. Nitric Oxide. 2008; 19 (Suppl.): S61.
52. Evgenov OV, Pacher P, Schmidt PM, Hasko G, Schmidt HH, Stasch JP (2006) NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potential. Nat Rev Drug Discov 5:755-768
53. Feil R, Kleppisch T (2008) NO/cGMP-dependent modulation of synaptic transmission. Handb Exp Pharmacol: 529-560
54. Fields LE, Burt VL, Cutler JA, Hughes J, Roccella EJ, Sorlie P (2004) The burden of adult hypertension in the United States 1999 to 2000: a rising tide. Hypertension 44:398-404
55. Filippi S, Morelli A, Sandner P, Fibbi B, Mancina R,MariniM, Gacci M, Vignozzi L, Vannelli GB, Carini M, Forti G,MaggiM(2007) Characterization and functional role of androgen-dependent PDE5 activity in the bladder. Endocrinology 148:1019-1029
56. Franco V, Oparil S (2006) Is there a new treatment for hypertensive disease in the horizon? Role of soluble guanylate cyclase. Hypertension 48:822-823
57. Freitas CF, Morganti RP, Annichino-Bizzacchi JM, De Nucci G, Antunes E (2007) Effect of BAY 41-2272 in the pulmonary hypertension induced by heparin-protamine complex in anaesthetized dogs. Clin Exp Pharmacol Physiol 34:10-14
58. Frey R, Mück W, Unger S, Artmeier-Brandt U, Weimann G, Wensing G (2008) Single-dose pharmacokinetics, pharmacodynamics, tolerability and safety of the soluble guanylate cyclase stimulator BAY 63-2521: an ascending-dose study in healthy male volunteers. J Clin Pharmacol 48:926-934
59. Friebe A, Koesling D (1998) Mechanism of YC-1-induced activation of soluble guanylyl cyclase. Mol Pharmacol 53:123-127
60. Friebe A, Mullershausen F, Smolenski A, Walter U, Schultz G, Koesling D (1998) YC-1 potentiates nitric oxide- and carbon monoxide-induced cyclic GMP effects in human platelets. Mol Pharmacol 54:962-967
61. Friebe A, Russwurm M, Mergia E, Koesling D (1999) A point-mutated guanylyl cyclase with features of the YC-1-stimulated enzyme: implications for the YC-1 binding site? Biochemistry 38:15253-15257
62. Friebe A, Schultz G, Koesling D (1996) Sensitizing soluble guanylyl cyclase to become a highly CO-sensitive enzyme. EMBO J 15:6863-6868
63. Friebe A,Wedel B, Harteneck C, Foerster J, Schultz G, Koesling D (1997) Functions of conserved cysteines of soluble guanylyl cyclase. Biochemistry 36:1194-1198
64. Gaedeke J, Neumayer HH, Peters H (2006) Pharmacological management of renal fibrotic disease. Expert Opin Pharmacother 7:377-386
65. Gaine SP, Rubin LJ (1998) Primary pulmonary hypertension. Lancet 352:719-725
66. Galle J, Zabel U, Hubner U, Hatzelmann A, Wagner B, Wanner C, Schmidt HH (1999) Effects of the soluble guanylyl cyclase activator, YC-1, on vascular tone, cyclic GMP levels and phosphodiesterase activity. Br J Pharmacol 127:195-203
67. Garthwaite J. Concepts of neural nitric oxide-mediated transmission (2008). Eur J Neurosci. 27:2783-2802
68. Garthwaite G, Goodwin DA, Neale S, Riddall D, Garthwaite J (2002) Soluble guanylyl cyclase activator YC-1 protects white matter axons from nitric oxide toxicity and metabolic stress, probably through Na(+) channel inhibition. Mol Pharmacol 61:97-104
69. Ghofrani HA, Osterloh IH, Grimminger F (2006) Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond. Nat Rev Drug Discov 5:689-702
70. Ghofrani HA,Weimann G, Frey R, Voswinckel R, Thamm M, Bölkow D,Weissmann N, Mück W, Unger S,Wensing G, Schermuly R, Grimminger F (2007) BAY 63-2521, an oral soluble guanylate cyclase stimulator, has a favourable safety profile, improves cardiopulmonary haemodynamics and has therapeutic potential in pulmonary hypertension. BMC Pharmacology 7:S8
71. Giaid A, Saleh D (1995) Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N Engl J Med 333:214-221
72. GISSI-3 (1994) GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell'infarto Miocardico. Lancet 343:1115-1122
73. Gladwin MT (2006) Deconstructing endothelial dysfunction: soluble guanylyl cyclase oxidation and the NO resistance syndrome. J Clin Invest 116:2330-2332
74. Gonzalez-Luis G, Cogolludo A, Moreno L, Lodi F, Tamargo J, Perez-Vizcaino F, Villamor E (2006) Relaxant effects of the soluble guanylate cyclase activator and NO sensitizer YC-1 in piglet pulmonary arteries. Biol Neonate 90:66-72
75. Gupte SA, Rupawalla T, Phillibert D Jr, Wolin MS (1999) NADPH and heme redox modulate pulmonary artery relaxation and guanylate cyclase activation by NO. Am J Physiol 277:L1124-L1132
76. Handy DE, Loscalzo J (2006) Nitric oxide and posttranslational modification of the vascular proteome: S-nitrosation of reactive thiols. Arterioscler Thromb Vasc Biol 26:1207-1214
77. Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352:1685-1695
78. Hare JM, Stamler JS (2005) NO/redox disequilibrium in the failing heart and cardiovascular system. J Clin Invest 115:509-517
79. Harrison DG, Cai H, Landmesser U, Griendling KK (2003) Interactions of angiotensin II with NAD(P)H oxidase, oxidant stress and cardiovascular disease. J Renin Angiotensin Aldosterone Syst 4:51-61
80. Hering KW, Artz JD, Pearson WH, Marletta MA (2006) The design and synthesis of YC-1 analogues as probes for soluble guanylate cyclase. Bioorg Med Chem Lett 16:618-621
81. Hobbs AJ (2002) Soluble guanylate cyclase: an old therapeutic target re-visited. Br J Pharmacol 136:637-640
82. Hobbs AJ, Moncada S (2003) Antiplatelet properties of a novel, non-NO-based soluble guanylate cyclase activator, BAY 41-2272. Vascul Pharmacol 40:149-154
83. Hoenicka M, Becker EM, Apeler H, Sirichoke T, Schroder H, Gerzer R, Stasch JP (1999) Purified soluble guanylyl cyclase expressed in a baculovirus/Sf9 system: stimulation by YC-1, nitric oxide, and carbon monoxide. J Mol Med 77:14-23
84. Hohenstein B, Daniel C, Wagner A, Stasch JP, Hugo C (2005) Stimulation of soluble guanylyl cyclase inhibits mesangial cell proliferation and matrix accumulation in experimental glomerulonephritis. Am J Physiol Renal Physiol 288:F685-F693
85. Hsieh GC, O'Neill AB, Moreland RB, Sullivan JP, Brioni JD (2003) YC-1 potentiates the nitric oxide/cyclic GMP pathway in corpus cavernosum and facilitates penile erection in rats. Eur J Pharmacol 458:183-189
86. Hsu HK, Juan SH, Ho PY, Liang YC, Lin CH, Teng CM, Lee WS (2003) YC-1 inhibits proliferation of human vascular endothelial cells through a cyclic GMP-independent pathway. Biochem Pharmacol 66:263-271
87. Huang YT, Pan SL, Guh JH, Chang YL, Lee FY, Kuo SC, Teng CM (2005) YC-1 suppresses constitutive nuclear factor-kappaB activation and induces apoptosis in human prostate cancer cells. Mol Cancer Ther 4:1628-1635
88. Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver MA, Stevenson LW, Yancy CW, Antman EM, Smith SC, Jr., Adams CD, Anderson JL, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B (2005) ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation 112:e154-e235
89. Hussain MB, Hobbs AJ, MacAllister RJ (1999) Autoregulation of nitric oxide-soluble guanylate cyclase-cyclic GMP signalling in mouse thoracic aorta. Br J Pharmacol 128:1082-1088
90. Hwang TL, Wu CC, Guh JH, Teng CM (2003) Potentiation of tumor necrosis factor-alpha expression by YC-1 in alveolar macrophages through a cyclic GMP-independent pathway. Biochem Pharmacol 66:149-156
91. Ichinose F, Roberts JD, Jr., ZapolWM(2004) Inhaled nitric oxide: a selective pulmonary vasodilator: current uses and therapeutic potential. Circulation 109:3106-3111
92. Ignarro LJ, Bush PA, Buga GM, Wood KS, Fukuto JM, Rajfer J (1990) Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle. Biochem Biophys Res Commun 170:843-850
93. ISIS-4 Collaborative Group (1995) ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. Lancet 345:669-685
94. Jackson EB Jr, Mukhopadhyay S, Tulis DA (2007) Pharmacologic modulators of soluble guanylate cyclase/cyclic guanosine monophosphate in the vascular system - from bench top to bedside. Curr Vasc Pharmacol 5:1-14
95. Kagota S, Yamaguchi Y, Tanaka N, Kubota Y, Kobayashi K, Nejime N, Nakamura K, Kunitomo M, Shinozuka K (2006) Disturbances in nitric oxide/cyclic guanosine monophosphate system in SHR/NDmcr-cp rats, a model of metabolic syndrome. Life Sci 78:1187-1196
96. Kalsi JS, Ralph DJ, Madge DJ, Kell PD, Cellek S (2004) A comparative study of sildenafil, NCX-911 and BAY41-2272 on the anococcygeus muscle of diabetic rats. Int J Impot Res 16:479-485
97. Kalsi JS, Rees RW, Hobbs AJ, Royle M, Kell PD, Ralph DJ, Moncada S, Cellek S (2003) BAY41-2272, a novel nitric oxide independent soluble guanylate cyclase activator, relaxes human and rabbit corpus cavernosum in vitro. J Urol 169:761-766
98. Kessler R, Faller M, Weitzenblum E, Chaouat A, Aykut A, Ducolone A, Ehrhart M, Oswald- Mammosser M (2001) Natural history of pulmonary hypertension in a series of 131 patients with chronic obstructive lung disease. Am J Respir Crit Care Med 164:219-224
99. Kharitonov VG, Sharma VS, Magde D, Koesling D (1999) Kinetics and equilibria of soluble guanylate cyclase ligation by CO: effect of YC-1. Biochemistry 38:10699-10706
100. Kim D, Rybalkin SD, Pi X, Wang Y, Zhang C, Munzel T, Beavo JA, Berk BC, Yan C (2001) Upregulation of phosphodiesterase 1A1 expression is associated with the development of nitrate tolerance. Circulation 104:2338-2343
101. Klinger JR, Thaker S, Houtchens J, Preston IR, Hill NS, Farber HW (2006) Pulmonary hemodynamic responses to brain natriuretic peptide and sildenafil in patients with pulmonary arterial hypertension. Chest 129:417-425
102. Kloss S, Bouloumie A, Mulsch A (2000) Aging and chronic hypertension decrease expression of rat aortic soluble guanylyl cyclase. Hypertension 35:43-47
103. Knorr A, Hirth-Dietrich C, Alonso-Alija C, Härter M, Hahn M, Keim Y, Wunder F, Stasch JP (2008) Nitric oxide-independent activation of soluble guanylate cyclase by BAY 60-2770 in experimental liver fibrosis. Arzneimittelforschung 58:71-80
104. Ko FN, Wu CC, Kuo SC, Lee FY, Teng CM (1994) YC-1, a novel activator of platelet guanylate cyclase. Blood 84:4226-4233
105. Koenig G, Schreiber R,Wunder F, Stasch JP, Stahl E, Luithle J, Feurer A,Wirtz SN, Lang D (2004) 4-amino-substituted pyrimidine derivatives. USA; CA2492726
106. Koglin M, Behrends S (2003) A functional domain of the alpha1 subunit of soluble guanylyl cyclase is necessary for activation of the enzyme by nitric oxide and YC-1 but is not involved in heme binding. J Biol Chem 278:12590-12597
107. Koglin M, Stasch JP, Behrends S (2002) BAY 41-2272 activates two isoforms of nitric oxidesensitive guanylyl cyclase. Biochem Biophys Res Commun 292:1057-1062
108. Kojda G, Kottenberg K, Hacker A, Noack E (1998) Alterations of the vascular and the myocardial guanylate cyclase/cGMP-system induced by long-term hypertension in rats. Pharm Acta Helv 73:27-35
109. Krasuski RA, Warner JJ, Wang A, Harrison JK, Tapson VF, Bashore TM (2000) Inhaled nitric oxide selectively dilates pulmonary vasculature in adult patients with pulmonary hypertension, irrespective of etiology. J Am Coll Cardiol 36:2204-2211
110. Kung HC, Hoyert DL, Xu J, Murphy SL (2007) Deaths: Preliminary Data for 2005. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics, Hyattsville, MD. http://www.cdc.gov/nchs/products/pubs/pubd/hestats/prelimdeaths05/ prelimdeaths05.htm, accessed 24 January 2008
111. Lamothe M, Chang FJ, Balashova N, Shirokov R, Beuve A (2004) Functional characterization of nitric oxide and YC-1 activation of soluble guanylyl cyclase: structural implication for the YC-1 binding site? Biochemistry 43:3039-3048
112. Lau CK, Yang ZF, Lam CT, Tam KH, Poon RT, Fan ST (2006) Suppression of hypoxia inducible factor-1alpha (HIF-1alpha) by YC-1 is dependent on murine double minute 2 (Mdm2). Biochem Biophys Res Commun 348:1443-1448
113. Layish DT, Tapson VF (1997) Pharmacologic hemodynamic support in massive pulmonary embolism. Chest 111:218-224
114. Lee FY, Lien JC, Huang LJ, Huang TM, Tsai SC, Teng CM, Wu CC, Cheng FC, Kuo SC (2001) Synthesis of 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole analogues as novel antiplatelet agents. J Med Chem 44:3746-3749
115. Lee YC, Martin E, Murad F (2000) Human recombinant soluble guanylyl cyclase: expression, purification, and regulation. Proc Natl Acad Sci U S A 97:10763-10768
116. Li Y, Zhang D, Jin W, Shao C, Yan P, Xu C, Sheng H, Liu Y, Yu J, Xie Y, Zhao Y, Lu D, Nebert DW, Harrison DC, HuangW, Jin L (2006) Mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys polymorphism contributes to the variation in efficacy of sublingual nitroglycerin J Clin Invest 116:506-511
117. Liu YN, Pan SL, Peng CY, Guh JH, Huang DM, Chang YL, Lin CH, Pai HC, Kuo SC, Lee FY, Teng CM (2006) YC-1 [3-(5-hydroxymethyl-2-furyl)-1-benzyl indazole] inhibits neointima formation in balloon-injured rat carotid through suppression of expressions and activities of matrix metalloproteinases 2 and 9. J Pharmacol Exp Ther 316:35-41
118. Liu YN, Pan SL, Peng CY, Huang DY, Guh JH, Kuo SC, Lee FY, Teng CM (2008) YC-1 induces heat shock protein 70 expression and prevents oxidized Ldl-mediated apoptosis in vascular smooth muscle cells. Shock 30:274-279
119. Lu DY, Tang CH, Liou HC, Teng CM, Jeng KC, Kuo SC, Lee FY, Fu WM (2007) YC-1 attenuates LPS-induced proinflammatory responses and activation of nuclear factor-kappaB in microglia. Br J Pharmacol 151:396-405
120. Luithle J, Koenig G, Stasch JP, Stahl E, Wirtz SN, Lang D, Feurer A, Schenke T, Wunder F, Schreiber R (2004) Morpholine-bridged indazole derivatives. USA; CA2500088
121. Luscher TF, BartonM (2000) Endothelins and endothelin receptor antagonists: therapeutic considerations for a novel class of cardiovascular drugs. Circulation 102:2434-2440
122. Ma X, Sayed N, Beuve A, van den Akker F (2007) NO and CO differentially activate soluble guanylyl cyclase via a heme pivot-bend mechanism. EMBO J 26:578-588
123. MacPherson JD, Gillespie TD, Dunkerley HA, Maurice DH, Bennett BM (2006) Inhibition of phosphodiesterase 5 selectively reverses nitrate tolerance in the venous circulation. J Pharmacol Exp Ther 317:188-195
124. Makino R, Obayashi E, Homma N, Shiro Y, Hori H (2003) YC-1 facilitates release of the proximal His residue in the NO and CO complexes of soluble guanylate cyclase. J Biol Chem 278:11130-11137
125. Martin NI, Derbyshire ER, Marletta MA (2007) Synthesis and evaluation of a phosphonate analogue of the soluble guanylate cyclase activator YC-1. Bioorg Med Chem Lett 17:4938-4941
126. Masuyama H, Tsuruda T, Kato J, Imamura T, Asada Y, Stasch JP, Kitamura K, Eto T (2006) Soluble guanylate cyclase stimulation on cardiovascular remodeling in angiotensin II-induced hypertensive rats. Hypertension 48:972-978
127. Mayer B, Beretta M (2008) The enigma of nitroglycerin bioactivation and nitrate tolerance: news, views and troubles. Br J Pharmacol 155:170-184
128. McLaughlin BE, Chretien ML, Choi C, Brien JF, Nakatsu K, Marks GS (2000) Potentiation of carbon monoxide-induced relaxation of rat aorta by YC-1 [3-(5 c-hydroxymethyl-2 c-furyl)-1-benzylindazole]. Can J Physiol Pharmacol 78: 343-349
129. Melichar VO, Behr-Roussel D, Zabel U, Uttenthal LO, Rodrigo J, Rupin A, Verbeuren TJ, Kumar HSA, Schmidt HH (2004) Reduced cGMP signaling associated with neointimal proliferation and vascular dysfunction in late-stage atherosclerosis. Proc Natl Acad Sci U S A 101:16671-16676
130. Mergia E, Russwurm M, Zoidl G, Koesling D (2003) Major occurrence of the new alpha2beta1 isoform of NO-sensitive guanylyl cyclase in brain. Cell Signal 15:189-195
131. Messerli FH, Williams B, Ritz E (2007) Essential hypertension. Lancet 370:591-603
132. Mingone CJ, Ahmad M, Gupte SA, Chow JL, Wolin MS (2008) Heme oxygenase-1 induction depletes heme and attenuates pulmonary artery relaxation and guanylate cyclase activation by nitric oxide. Am J Physiol Heart Circ Physiol 294:H1244-H1250
133. Miller LN, Nakane M, Hsieh GC, Chang R, Kolasa T, Moreland RB, Brioni JD (2003) A-350619: a novel activator of soluble guanylyl cyclase. Life Sci 72: 1015-1025
134. Mizusawa H, Hedlund P, Brioni JD, Sullivan JP, Andersson KE (2002) Nitric oxide independent activation of guanylate cyclase by YC-1 causes erectile responses in the rat. J Urol 167:2276-2281
135. Morawietz H, Weber M, Rueckschloss U, Lauer N, Hacker A, Kojda G (2001) Upregulation of vascular NAD(P)H oxidase subunit gp91phox and impairment of the nitric oxide signal transduction pathway in hypertension. Biochem Biophys Res Commun 285: 1130-1135
136. Mullershausen F, Russwurm M, Friebe A, Koesling D (2004) Inhibition of phosphodiesterase type 5 by the activator of nitric oxide-sensitive guanylyl cyclase BAY 41-2272. Circulation 109:1711-1713
137. Mulsch A, Bara A, Mordvintcev P, Vanin A, Busse R (1995) Specificity of different organic nitrates to elicit NO formation in rabbit vascular tissues and organs in vivo. Br J Pharmacol 116:2743-2749
138. Mulsch A, Bauersachs J, Schafer A, Stasch JP, Kast R, Busse R (1997) Effect of YC-1, an NOindependent, superoxide-sensitive stimulator of soluble guanylyl cyclase, on smooth muscle responsiveness to nitrovasodilators. Br J Pharmacol 120:681-689
139. Mulsch A, Oelze M, Kloss S, Mollnau H, Topfer A, Smolenski A, Walter U, Stasch JP, Warnholtz A, Hink U, Meinertz T, Munzel T (2001) Effects of in vivo nitroglycerin treatment on activity and expression of the guanylyl cyclase and cGMP-dependent protein kinase and their downstream target vasodilator-stimulated phosphoprotein in aorta. Circulation 103: 2188-2194
140. Munzel T, Daiber A, Mulsch A (2005) Explaining the phenomenon of nitrate tolerance. Circ Res 97:618-628
141. Munzel T, Genth-Zotz S, Hink U (2007) Targeting heme-oxidized soluble guanylate cyclase: solution for all cardiorenal problems in heart failure? Hypertension 49:974-976
142. Murad F (2006) Shattuck lecture. Nitric oxide and cyclic GMP in cell signaling and drug development. N Engl J Med 355:2003-2011
143. Murray CJ, Lopez AD (1997) Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet 349:1498-1504
144. Nagayama T, Zhang M, Hsu S, Takimoto E, Kass DA (2008) Sustained soluble guanylate cyclase stimulation offsets nitric-oxide synthase inhibition to restore acute cardiac modulation by sildenafil. J Pharmacol Exp Ther. 326:380-387
145. Nakane M (2003) Soluble guanylyl cyclase: physiological role as an NO receptor and the potential molecular target for therapeutic application. Clin Chem Lab Med 41:865-870
146. Nakane M, Hsieh G, Miller LN, Chang R, Terranova MA, Moreland RB, Kolasa T, Brioni JD (2002) Activation of soluble guanylate cyclase causes relaxation of corpus cavernosum tissue:synergism of nitric oxide and YC-1. Int J Impot Res 14:121-127
147. Nakane M, Kolasa T, Chang R, Miller LN, Moreland RB, Brioni JD (2006) Acrylamide analog as a novel nitric oxide-independent soluble guanylyl cyclase activator. J Pharmacol Sci 102:231-238
148. National Institutes of Health (1993) Consensus development conference statement. National Institutes of Health. Impotence. December 7-9, 1992. Int J Impot Res 5:181-284
149. Nguyen T, Brunson D, Crespi CL, Penman BW, Wishnok JS, Tannenbaum SR (1992) DNA damage and mutation in human cells exposed to nitric oxide in vitro. Proc Natl Acad Sci U S A 89:3030-3034
150. O'Donnell VB, Freeman BA (2001) Interactions between nitric oxide and lipid oxidation pathways: implications for vascular disease. Circ Res 88:12-21
151. Olschewski H, Walmrath D, Schermuly R, Ghofrani A, Grimminger F, Seeger W (1996) Aerosolized prostacyclin and iloprost in severe pulmonary hypertension. Ann Intern Med 124:820-824
152. O'Reilly DA, McLaughlin BE, Marks GS, Brien JF, Nakatsu K (2001) YC-1 enhances the responsiveness of tolerant vascular smooth muscle to glyceryl trinitrate. Can J Physiol Pharmacol 79:43-48
153. Pacher P, Schulz R, Liaudet L, Szabo C (2005) Nitrosative stress and pharmacological modulation of heart failure. Trends Pharmacol Sci 26:302-310
154. Pagani ED, VanAller GS, O'Connor B, Silver PJ (1993) Reversal of nitroglycerin tolerance in vitro by the cGMP-phosphodiesterase inhibitor zaprinast. Eur J Pharmacol 243:141-147
155. Pan SL, Guh JH, Chang YL, Kuo SC, Lee FY, Teng CM (2004) YC-1 prevents sodium nitroprusside-mediated apoptosis in vascular smooth muscle cells. Cardiovasc Res 61:152-158
156. Pan SL, Guh JH, Peng CY, Chang YL, Cheng FC, Chang JH, Kuo SC, Lee FY, Teng CM (2005a) A potential role of YC-1 on the inhibition of cytokine release in peripheral blood mononuclear leukocytes and endotoxemic mouse models. Thromb Haemost 93:940-948
157. Pan SL, Guh JH, Peng CY, Wang SW, Chang YL, Cheng FC, Chang JH, Kuo SC, Lee FY, Teng CM (2005b) YC-1 [3-(5-hydroxymethyl-2-furyl)-1-benzyl indazole] inhibits endothelial cell functions induced by angiogenic factors in vitro and angiogenesis in vivo models. J Pharmacol Exp Ther 314:35-42
158. Patel NM, Lederer DJ, Borczuk AC, Kawut SM (2007) Pulmonary hypertension in idiopathic pulmonary fibrosis. Chest 132:998-1006
159. Pauwels RA, Rabe KF (2004) Burden and clinical features of chronic obstructive pulmonary disease (COPD). Lancet 364:613-620
160. Peacock AJ (2003) Treatment of pulmonary hypertension. BMJ 326:835-836
161. Pellicena P, Karow DS, Boon EM, Marletta MA, Kuriyan J (2004) Crystal structure of an oxygenbinding heme domain related to soluble guanylate cyclases. Proc Natl Acad Sci U S A 101:12854-12859
162. Peters H, Daig U, Martini S, Ruckert M, Schaper F, Liefeldt L, Kramer S, Neumayer HH (2003) NO mediates antifibrotic actions of L-arginine supplementation following induction of antithy1 glomerulonephritis. Kidney Int 64:509-518
163. Peters H,Wang Y, Loof T, Martini S, Kron S, Kramer S, Neumayer HH (2004) Expression and activity of soluble guanylate cyclase in injury and repair of anti-thy1 glomerulonephritis. Kidney Int 66:2224-2236
164. Phoa N, Epe B (2002) Influence of nitric oxide on the generation and repair of oxidative DNA damage in mammalian cells. Carcinogenesis 23:469-475
165. Postma DS, Timens W (2006) Remodeling in asthma and chronic obstructive pulmonary disease. Proc Am Thorac Soc 3:434-439
166. Prins J, Blanker MH, Bohnen AM, Thomas S, Bosch JL (2002) Prevalence of erectile dysfunction: a systematic review of population-based studies. Int J Impot Res 14:422-432
167. Pyriochou A, Beis D, Koika V, Potytarchou C, Papadimitriou E, Zhou Z, Papapetropoulos A (2006) Soluble guanylyl cyclase activation promotes angiogenesis. J Pharmacol Exp Ther 319:663-671
168. Radi R (2004) Nitric oxide, oxidants, and protein tyrosine nitration. Proc Natl Acad Sci U S A 101:4003-4008
169. Radi R, Cassina A, Hodara R (2002) Nitric oxide and peroxynitrite interactions with mitochondria. Biol Chem 383:401-409
170. Rajfer J, Aronson WJ, Bush PA, Dorey FJ, Ignarro LJ (1992) Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission. N Engl J Med 326:90-94
171. Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, Haase N, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D,McDermott M, Meigs J,Moy C, Nichol G, O'Donnell CJ, Roger V, Rumsfeld J, Sorlie P, Steinberger J, Thom T, Wasserthiel-Smoller S, Hong Y (2007) Heart disease and stroke statistics-2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 115:e69-e171
172. Rothermund L, Friebe A, Paul M, Koesling D, Kreutz R (2000) Acute blood pressure effects of YC-1-induced activation of soluble guanylyl cyclase in normotensive and hypertensive rats. Br J Pharmacol 130:205-208
173. Roy B, Garthwaite J (2006) Nitric oxide activation of guanylyl cyclase in cells revisited. Proc Natl Acad Sci U S A 103:12185-12190
174. Ruetten H, Zabel U, Linz W, Schmidt HH (1999) Downregulation of soluble guanylyl cyclase in young and aging spontaneously hypertensive rats. Circ Res 85:534-541
175. Russwurm M, Koesling D (2004) NO activation of guanylyl cyclase. EMBO J 23:4443-4450
176. Russwurm M, Mergia E, Mullershausen F, Koesling D (2002) Inhibition of deactivation of NOsensitive guanylyl cyclase accounts for the sensitizing effect of YC-1. J Biol Chem 277:24883-24888
177. Sandner P, Hutter J, Tinel H, Ziegelbauer K, Bischoff E (2007) PDE5 inhibitors beyond erectile dysfunction. Int J Impot Res 19:533-543
178. Schermuly RT, Stasch JP, Pullamsetti SS, Middendorff R, Mueller HD, Schlüter KD, Dingendorf A, Kolosionek E, Kaulen C, Dumitrascu R, Weissmann N, Mittendorf J, KlepetkoW, Seeger W, Ghofrani HA, Grimminger F (2008) Expression and function of soluble guanylate cyclase in pulmonary arterial hypertension. Eur Respir J 32:881-891
179. Schmidt K, Schrammel A, Koesling D, Mayer B (2001) Molecular mechanisms involved in the synergistic activation of soluble guanylyl cyclase by YC-1 and nitric oxide in endothelial cells. Mol Pharmacol 59:220-224
180. Schmidt P, Schramm M, Schroder H, Stasch JP (2003) Mechanisms of nitric oxide independent activation of soluble guanylyl cyclase. Eur J Pharmacol 468:167-174
181. Schmidt PM, Rothkegel C,Wunder F, Schroder H, Stasch JP (2005) Residues stabilizing the heme moiety of the nitric oxide sensor soluble guanylate cyclase. Eur J Pharmacol 513:67-74
182. Schmidt PM, Schramm M, Schroder H, Wunder F, Stasch JP (2004) Identification of residues crucially involved in the binding of the heme moiety of soluble guanylate cyclase. J Biol Chem 279:3025-3032
183. Selwood DL, Brummell DG, Budworth J, Burtin GE, Campbell RO, Chana SS, Charles IG, Fernandez PA, Glen RC, Goggin MC, Hobbs AJ, Kling MR, Liu Q, Madge DJ, Meillerais S, Powell KL, Reynolds K, Spacey GD, Stables JN, Tatlock MA, Wheeler KA, Wishart G, Woo CK (2001) Synthesis and biological evaluation of novel pyrazoles and indazoles as activators of the nitric oxide receptor, soluble guanylate cyclase. J Med Chem 44:78-93
184. Sharma VS, Magde D, Kharitonov VG, Koesling D (1999) Soluble guanylate cyclase: effect of YC-1 on ligation kinetics with carbon monoxide. Biochem Biophys Res Commun 254: 188-191
185. Shin DH, Kim JH, Jung YJ, Kim KE, Jeong JM, Chun YS, Park JW (2007) Preclinical evaluation of YC-1, a HIF inhibitor, for the prevention of tumor spreading. Cancer Lett 255:107-116
186. Simonneau G, Galie N, Rubin LJ, Langleben D, Seeger W, Domenighetti G, Gibbs S, Lebrec D, Speich R, Beghetti M, Rich S, Fishman A (2004) Clinical classification of pulmonary hypertension. J Am Coll Cardiol 43:5S-12S
187. Slupski M, Szadujkis-Szadurski L, Grzesk G, Szadujkis-Szadurski R, Szadujkis-Szadurska K, Wlodarczyk Z, Masztalerz M, Piotrowiak I, Jasinski M (2007) Guanylate cyclase activators influence reactivity of human mesenteric superior arteries retrieved and preserved in the same conditions as transplanted kidneys. Transplant Proc 39:1350-1353
188. Smulders YM (2000) Pathophysiology and treatment of haemodynamic instability in acute pulmonary embolism: the pivotal role of pulmonary vasoconstriction. Cardiovasc Res 48:23-33
189. Speich R, Jenni R, Opravil M, Pfab M, Russi EW (1991) Primary pulmonary hypertension in HIV infection. Chest 100:1268-1271
190. Stahl E, Feurer A, Luithle J,Wirtz SN,Wunder F, Schreiber R, Stasch JP, Lang D, Koenig G (2004) Novel 2,5-distributed pyrimidine derivatives. USA; CA2492723
191. Stasch JP, Alonso-Alija C, Apeler H, Dembowsky K, Feurer A, Minuth T, Perzborn E, Schramm M, Straub A (2002a) Pharmacological actions of a novel NO-independent guanylyl cyclase stimulator, BAY 41-8543: in vitro studies. Br J Pharmacol 135:333-343
192. Stasch JP, Becker EM, Alonso-Alija C, Apeler H, Dembowsky K, Feurer A, Gerzer R, Minuth T, Perzborn E, Pleiss U, Schroder H, Schroeder W, Stahl E, Steinke W, Straub A, Schramm M (2001) NO-independent regulatory site on soluble guanylate cyclase. Nature 410:212-215
193. Stasch JP, Dembowsky K, Perzborn E, Stahl E, Schramm M (2002b) Cardiovascular actions of a novel NO-independent guanylyl cyclase stimulator, BAY 41-8543: in vivo studies. Br J Pharmacol 135:344-355
194. Stasch JP, Schmidt PM, Nedvetsky PI, Nedvetskaya TY, HSA, Meurer S, Deile M, Taye A, Knorr A, Lapp H, Muller H, Turgay Y, Rothkegel C, Tersteegen A, Kemp-Harper B,young and aging spontaneously hypertensive rats. Circ Res 85:534-541
195. Muller-Esterl W, Schmidt HH (2006) Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of diseased blood vessels. J Clin Invest 116:2552-2561
196. Stone JR, Marletta MA (1994) Soluble guanylate cyclase from bovine lung: activation with nitric oxide and carbon monoxide and spectral characterization of the ferrous and ferric states.Biochemistry 33:5636-5640
197. Stone JR,MarlettaMA (1998) Synergistic activation of soluble guanylate cyclase by YC-1 and carbon monoxide: implications for the role of cleavage of the iron-histidine bond during activation by nitric oxide. Chem Biol 5:255-261
198. Straub A, Benet-Buckholz J, Frode R, Kern A, Kohlsdorfer C, Schmitt P, Schwarz T, Siefert HM, Stasch JP (2002) Metabolites of orally active NO-independent pyrazolopyridine stimulators of soluble guanylate cyclase. Bioorg Med Chem 10:1711-1717
199. Straub A, Stasch JP, Alonso-Alija C, Benet-Buchholz J, Ducke B, Feurer A, Furstner C (2001) NO-independent stimulators of soluble guanylate cyclase. Bioorg Med Chem Lett 11:781-784
200. Strong JP, Malcom GT, McMahan CA, Tracy RE, Newman WP, 3rd, Herderick EE, Cornhill JF (1999) Prevalence and extent of atherosclerosis in adolescents and young adults: implications for prevention from the Pathobiological Determinants of Atherosclerosis in Youth Study. JAMA 281:727-735
201. Teixeira CE, Priviero FB, Claudino MA, Baracat JS, De Nucci G, Webb RC, Antunes E (2006a) Stimulation of soluble guanylyl cyclase by BAY 41-2272 relaxes anococcygeus muscle: interaction with nitric oxide. Eur J Pharmacol 530:157-165
202. Teixeira CE, Priviero FB, Webb RC (2006b) Molecular mechanisms underlying rat mesenteric artery vasorelaxation induced by the nitric oxide-independent soluble guanylyl cyclase stimulators BAY 41-2272 [5-cyclopropyl-2-[1-(2- fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimi din-4-ylamine] and YC-1 [3-(5-hydroxymethyl-2-furyl)-1-benzyl Indazole]. J Pharmacol Exp Ther 317:258-266
203. Teixeira CE, Priviero FB, Webb RC (2007) Effects of 5-Cyclopropyl-2-[1- (2-fluoro-benzyl)-1Hpyrazolo[ 3,4-b]pyridine-3-yl]pyrim idin-4-ylamine (BAY 41-2272) on smooth muscle tone, soluble guanylyl cyclase Activity, and NADPH oxidase activity/expression in corpus cavernosum from wild-type, neuronal, and endothelial nitric-oxide synthase null mice. J Pharmacol Exp Ther 322:1093-1102
204. Teng CM, Wu CC, Ko FN, Lee FY, Kuo SC (1997) YC-1, a nitric oxide-independent activator of soluble guanylate cyclase, inhibits platelet-rich thrombosis in mice. Eur J Pharmacol 320: 161-166
205. Tesmer JJ, Sunahara RK, Gilman AG, Sprang SR (1997) Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsalpha.GTPgammaS. Science 278:1907-1916
206. Thadani U, Ripley TL (2007) Side effects of using nitrates to treat heart failure and the acute coronary syndromes, unstable angina and acute myocardial infarction. Expert Opin Drug Saf 6:385-396
207. Tinel H, Stelte-Ludwig B, Hutter J, Sandner P (2006) Pre-clinical evidence for the use of phosphodiesterase-5 inhibitors for treating benign prostatic hyperplasia and lower urinary tract symptoms. BJU Int 98:1259-1263
208. Toque HA, Antunes E, Teixeira CE, De Nucci G. Increased cyclic guanosine monophosphate synthesis and calcium entry blockade account for the relaxant activity of the nitric oxideindependent soluble guanylyl cyclase stimulator BAY 41-2272 in the rabbit penile urethra. Urology. 2008 Sep; 72(3):711-5.
209. Tsai IF, Lin CY, Huang CT, Lin YC, Yang CM, Liao CH (2007) Modulation of human monocytederived dendritic cells maturation by a soluble guanylate cyclase activator, YC-1, in a cyclic nucleotide independent manner. Int Immunopharmacol 7:1299-1310
210. Tuder RM, Cool CD, Geraci MW, Wang J, Abman SH, Wright L, Badesch D, Voelkel NF (1999) Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am J Respir Crit Care Med 159:1925-1932
211. Tulis DA, Bohl Masters KS, Lipke EA, Schiesser RL, Evans AJ, Peyton KJ, Durante W, West JL, Schafer AI (2002) YC-1-mediated vascular protection through inhibition of smooth muscle cell proliferation and platelet function. Biochem Biophys Res Commun 291:1014-1021Tulis DA, DuranteW, Peyton KJ, Chapman GB, Evans AJ, Schafer AI (2000) YC-1, a benzyl indazole derivative, stimulates vascular cGMP and inhibits neointima formation. Biochem Biophys Res Commun 279:646-652
212. Ungvari Z, Gupte SA, Recchia FA, Batkai S, Pacher P (2005) Role of oxidative-nitrosative stress and downstream pathways in various forms of cardiomyopathy and heart failure. Curr Vasc Pharmacol 3:221-229
213. van Staveren WC, Markerink-van Ittersum M, Steinbusch HW, Behrends S, de Vente J (2005) Localization and characterization of cGMP-immunoreactive structures in rat brain slices after NOdependent and NO-independent stimulation of soluble guanylyl cyclase. Brain Res 1036:77-89
214. Wang JP, Chang LC, Huang LJ, Kuo SC (2001) Inhibition of extracellular Ca(2+) entry by YC-1, an activator of soluble guanylyl cyclase, through a cyclic GMP-independent pathway in rat neutrophils. Biochem Pharmacol 62:679-684
215. Wang SW, Pan SL, Guh JH, Chen HL, Huang DM, Chang YL, Kuo SC, Lee FY, Teng CM (2005a) YC-1 [3-(5-hydroxymethyl-2-furyl)-1-benzyl Indazole] exhibits a novel antiproliferative effect and arrests the cell cycle in G0-G1 in human hepatocellular carcinoma cells. J Pharmacol Exp Ther 312:917-925
216. Wang Y, Kramer S, Loof T, Martini S, Kron S, Kawachi H, Shimizu F, Neumayer HH, Peters H (2005b) Stimulation of soluble guanylate cyclase slows progression in anti-thy1-induced chronic glomerulosclerosis. Kidney Int 68:47-61
217. Wang Y, Kramer S, Loof T, Martini S, Kron S, Kawachi H, Shimizu F, Neumayer HH, Peters H (2006) Enhancing cGMP in experimental progressive renal fibrosis: soluble guanylate cyclase stimulation vs. phosphodiesterase inhibition. Am J Physiol Renal Physiol 290:F167-F176
218. Weimann J, Ullrich R, Hromi J, Fujino Y, Clark MW, Bloch KD, Zapol WM (2000) Sildenafil is a pulmonary vasodilator in awake lambs with acute pulmonary hypertension. Anesthesiology 92:1702-1712
219. Wharton J, Strange JW, Moller GM, Growcott EJ, Ren X, Franklyn AP, Phillips SC, Wilkins MR (2005) Antiproliferative effects of phosphodiesterase type 5 inhibition in human pulmonary artery cells. Am J Respir Crit Care Med 172:105-113
220. Winger JA, Derbyshire ER, Marletta MA (2007) Dissociation of nitric oxide from soluble guanylate cyclase and heme-nitric oxide/oxygen binding domain constructs. J Biol Chem 282: 897-907
221. Wu CC, Ko FN, Kuo SC, Lee FY, Teng CM (1995) YC-1 inhibited human platelet aggregation through NO-independent activation of soluble guanylate cyclase. Br J Pharmacol 116: 1973-1978
222. Wu CH, Chang WC, Chang GY, Kuo SC, Teng CM (2004) The inhibitory mechanism of YC-1, a benzyl indazole, on smooth muscle cell proliferation: an in vitro and in vivo study. J Pharmacol Sci 94:252-260
223. Wu SN, Hwang T, Teng CM, Li HF, Jan CR (2000) The mechanism of actions of 3-(5- (hydroxymethyl-2-furyl)-1-benzyl indazole (YC-1) on Ca(2+)-activated K(+) currents in GH(3) lactotrophs. Neuropharmacology 39:1788-1799
224. Wu SY, Pan SL, Chen TH, Liao CH, Huang DY, Guh JH, Chang YL, Kuo SC, Lee FY, Teng CM. (2008) YC-1 induces apoptosis of human renal carcinoma A498 cells in vitro and in vivo through activation of the JNK pathway. Br J Pharmacol 155:505-513
225. Yang Z, Ming XF (2006) Recent advances in understanding endothelial dysfunction in atherosclerosis. Clin Med Res 4:53-65
226. Yeo EJ, Chun YS, Cho YS, Kim J, Lee JC, Kim MS, Park JW (2003) YC-1: a potential anticancer drug targeting hypoxia-inducible factor 1. J Natl Cancer Inst 95:516-525
227. Yeo EJ, Chun YS, Park JW (2004) New anticancer strategies targeting HIF-1. Biochem Pharmacol 68:1061-1069
228. Yeo EJ, Ryu JH, Chun YS, Cho YS, Jang IJ, Cho H, Kim J, KimMS, Park JW (2006) YC-1 induces S cell cycle arrest and apoptosis by activating checkpoint kinases. Cancer Res 66:6345-6352
229. Yoshina S, Tanaka A, Kuo SC (1978) [Studies on heterocyclic compounds. XXXIV. Synthesis of furo[3,2-c]pyrazole derivatives. (2). Electrophilic substitution of 1,3-diphenylfuro[3,2-c] pyrazole (author's transl)]. Yakugaku Zasshi 98:204-209
230. Zanfolin M, Faro R, Araujo EG, Guaraldo AM, Antunes E, De Nucci G (2006) Protective effects of BAY 41-2272 (sGC stimulator) on hypertension, heart, and cardiomyocyte hypertrophy induced by chronic L-NAME treatment in rats. J Cardiovasc Pharmacol 47:391-395
231. Zhang HQ, Zhiren X, Teodozyj K, Dinges J (2003) A concise synthesis of ortho-substituted arylacrylamides - potent activators of soluble guanylate cyclase. Tetrahedron Lett 44:8661-8663
232. Zhao Q, Du J, Gu H, Teng X, Zhang Q, Qin H, Liu N (2007) Effects of YC-1 on hypoxia-inducible factor 1-driven transcription activity, cell proliferative vitality, and apoptosis in hypoxic human pancreatic cancer cells. Pancreas 34:242-247
233. Russwurm M, Koesling D (2004) NO activation of guanylyl cyclase. EMBO J 23:4443-4450