Contractile mechanisms in diabetes-related erectile dysfunction

Current Pharmaceutical Design

Volumn 11, Issue 31, 2005, Pages 3995-4010

  DiSanto, Michael E ^a  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

Calcium sensitization; cGMP dependent protein kinase; Corpus cavernosum smooth muscle; Diabetes; Endothelin; Erectile dysfunction; Myosin phosphorylation; Rho kinase

Indexed keywords

2 PYRIDYLCARBAMIC ACID 2 [[5 (2 METHOXYPHENOXY) 6 [[(4 ISOPROPYLPHENYL)SULFONYL]AMINO] 2 MORPHOLINO 4 PYRIMIDINYL]OXY]ETHYL ESTER; 4 (1 AMINOETHYL) N (4 PYRIDYL)CYCLOHEXANECARBOXAMIDE; ALPHA ACTIN; BMS 193884; BOSENTAN; CALCIUM ACTIVATED POTASSIUM CHANNEL; CALCIUM ION; CALDESMON; CALPONIN; CPI 17; CYCLIC GMP DEPENDENT PROTEIN KINASE; DIACYLGLYCEROL; ENDOTHELIN 1; ENDOTHELIN RECEPTOR ANTAGONIST; INTEGRIN LINKED KINASE; LY 379196; MITOGEN ACTIVATED PROTEIN KINASE; MYOSIN; MYOSIN LIGHT CHAIN; PHOSPHODIESTERASE V INHIBITOR; PROSTAGLANDIN F2 ALPHA; PROTEIN KINASE C; PROTEIN KINASE C INHIBITOR; RHO KINASE; RUBOXISTAURIN; SILDENAFIL; TADALAFIL; THROMBOXANE A2; TROPOMYOSIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; VARDENAFIL;

CLINICAL TRIAL; CORPUS CAVERNOSUM; DIABETES MELLITUS; DISEASE ASSOCIATION; DRUG EFFICACY; DRUG HALF LIFE; DRUG MECHANISM; DRUG RECEPTOR BINDING; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INHIBITION; ERECTILE DYSFUNCTION; HUMAN; IN VITRO STUDY; MALE; MUSCLE CONTRACTILITY; MUSCLE TONE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REVIEW; SMOOTH MUSCLE CONTRACTION; SMOOTH MUSCLE RELAXATION;

3',5'-CYCLIC-GMP PHOSPHODIESTERASE; DIABETES COMPLICATIONS; HUMANS; IMPOTENCE; MALE; MUSCLE CONTRACTION; MUSCLE, SMOOTH; PHOSPHODIESTERASE INHIBITORS; PHOSPHORIC DIESTER HYDROLASES;

EID: 27944488679     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161205774913417     Document Type: Review

References (184)

1. Andersson KE, Wagner G. Physiology of penile erection. Physiol Rev 1995; 75: 191-236.
2. Christ GJ. The penis as a vascular organ. The importance of corporal smooth muscle tone in the control of erection. Urol Clin North Am 1995; 22: 727-745.
3. DiSanto ME. Corpus cavernosum smooth muscle physiology: A role for sex hormones? J Androl 2003; 24: S6-S16.
4. Lavoisier P, Courtois F, Barres D, Blanchard M. Correlation between intracavernous pressure and contraction of the ischiocavernosus muscle in man. J Urol 1986; 136: 936-939.
5. McKinlay JB. The worldwide prevalence and epidemiology of erectile dysfunction. Int J Impot Res 2000; 12 Suppl 4: S6-S11.
6. Krane RJ, Goldstein I, Saenz de TI. Impotence. N Engl J Med 1989; 321: 1648-1659.
7. Fedele D, Bortolotti A, Coscelli C, Santeusanio F, Chatenoud L, Colli E, et al. Erectile dysfunction in type 1 and type 2 diabetics in Italy. On behalf of Gruppo Italiano Studio Deficit Erettile nei Diabetici. Int J Epidemiol 2000; 29: 524-531.
8. Porst H. IC351 (tadalafil, Cialis): update on clinical experience. Int J Impot Res 2002; 14: S57-S63.
9. Porst H, Rosen R, Padma-Nathan H, Goldstein I, Giuliano F, Ulbrich E, et al. The efficacy and tolerability of vardenafil, a new, oral, selective phosphodiesterase type 5 inhibitor, in patients with erectile dysfunction: the first at-home clinical trial. Int J Impot Res 2001; 13: 192-199.
10. Archer SL. Potassium channels and erectile dysfunction. Vasc Pharmacol 2002; 38: 61-71.
11. Melman A, Christ GJ. Integrative erectile biology. The effects of age and disease on gap junctions and ion channels and their potential value to the treatment of erectile dysfunction. Urol Clin North Am 2001; 28: 217-231.
12. Mills TM, Chitaley K, Lewis RW, Webb RC. Nitric oxide inhibits RhoA/Rho-kinase signaling to cause penile erection. Eur J Pharmacol 2002; 439: 173-174.
13. Chitaley K, Webb RC. Nitric oxide induces dilation of rat aorta via inhibition of rho-kinase signaling. Hypertension 2002; 39: 438-442.
14. Thompson RF, Langford GM. Myosin superfamily evolutionary history. Anat Rec 2002; 268: 276-289.
15. Adelstein RS, Eisenberg E. Regulation and kinetics of the actin-myosin-ATP interaction. Annu Rev Biochem 1980; 49: 921-956.
16. Burchardt T, Burchardt M, Karden J, Buttyan R, Shabsigh A, de la TA, et al. Reduction of endothelial and smooth muscle density in the corpora cavernosa of the streptozotocin induced diabetic rat. J Urol 2000; 164: 1807-1811.
17. Babij P, Periasamy M. Myosin heavy chain isoform diversity in smooth muscle is produced by differential RNA processing. J Mol Biol 1989; 210: 673-679.
18. Pyne GJ, Lalli MJ, Martin AF, Paul RJ. Role of C-terminal myosin heavy chain isoforms in smooth muscle function: Evidence from mice overexpressing SMaSM1. Biophys J 2002; 82:1735.
19. Rovner AS, Fagnant PM, Lowey S, Trybus KM. The carboxyl-terminal isoforms of smooth muscle myosin heavy chain determine thick filament assembly properties. J Cell Biol 2002; 156: 113-123.
20. Makino H, Kashihara N, Stigiyama H, Kanao K, Sekikawa T, Okamoto K, et al. Phenotypic modulation of the mesangium reflected by contractile proteins in diabetes. Diabetes 1996; 45: 488-495.
21. Nakamura T, Ebihara I, Fukui M, Makita Y, Tomino Y, Kimura K, et al. Effects of enalapril treatment on gene expression of smooth muscle myosin heavy chain isoforms in glomeruli of diabetic rats. Renal Physiol Bioch 1995; 18: 183-190.
22. Nagai I, Kuro-o M, Aikawa M, Watanabe M, Suzuki T, Yazaki Y. Smooth muscle myosin heavy chain expression in the arterial wall; a new viewpoint for vascular pathology. [Japanese]. Rinsho Byori - JPN J Clin Pathol 1995; 43: 337-341.
23. Chiavegato A, Scatena M, Roelofs M, Ferrarese P, Pauletto P, Passerini-Glazel G, et al. Cytoskeletal and cytocontractile protein composition of smooth muscle cells in developing and obstructed rabbit bladder. Exp Cell Res 1993; 207: 310-320.
24. DiSanto ME, Stein R, Chang S, Hypolite JA, Zheng Y, Zderic SA, et al. Alteration in expression of myosin isoforms in detrusor smooth muscle following bladder outlet obstruction. Am J Physiol 2003; 285: C1397-C1410.
25. Wang ZE, Gopalakurup SK, Levin RM, Chacko S. Expression of smooth muscle myosin isoforms in urinary bladder smooth muscle during hypertrophy and regression. Lab Invest 1995; 73: 244-251.
26. Cher ML, Abernathy BB, McConnell JD, Zimmern PE, Lin VK. Smooth-muscle myosin heavy-chain isoform expression in bladder-outlet obstruction. World J Urol 1996; 14: 295-300.
27. Babij P, Kelly C, Periasamy M. Characterization of a mammalian smooth muscle myosin heavy-chain gene: complete nucleotide and protein coding sequence and analysis of the 5′ end of the gene. P Natl Acad Sci USA 1991; 88: 10676-10680.
28. Babij P. Tissue-specific and developmentally regulated alternative splicing of a visceral isoform of smooth muscle myosin heavy chain. Nucleic Acids Res 1993; 21: 1467-1471.
29. Kelley CA, Takahashi M, Yu JH, Adelstein RS. An insert of seven amino acids confers functional differences between smooth muscle myosins from the intestines and vasculature. J Biol Chem 1993; 268: 12848-12854.
30. 2-terminal-inserted myosin II heavy chain is expressed in smooth muscle of small muscular arteries. Am J Physiol 1997; 272: C1532-C1542.
31. Babu GJ, Loukianov E, Loukianova T, Pyne GJ, Huke S, Osol G, et al. Loss of SM-B myosin affects muscle shortening velocity and maximal force development. Nat Cell Biol 2001; 3: 1025-1029.
32. DiSanto ME, Wang Z, Menon C, Zheng Y, Chacko T, Hypolite J, et al. Expression of Myosin Isoforms in Smooth Muscle Cells in the Corpus Cavernosum Penis. Am J Physiol 1998; 275: C976-C987.
33. Chang S, Hypolite JA, Zderic SA, Wein AJ, Chacko S, DiSanto ME. Enhanced force generation by corpus cavernosum smooth muscle in rabbits with partial bladder outlet obstruction. J Urol 2002; 167: 2636-2644.
34. Chacko SK, DiSanto ME, Wein AJ. Changes in the composition of myosin isoforms in smooth muscle hypertrophy following urinary bladder outlet obstruction. Adv Organ Biol 2000; 8: 81-100.
35. Sato N, Komatsu K, Kurumatani H. Late onset of diabetic nephropathy in spontaneously diabetic GK rats. Am J Nephrol 2003; 23: 334-342.
36. Young BA, Johnson RJ, Alpers CE, Eng E, Gordon K, Floege J, et al. Cellular events in the evolution of experimental diabetic nephropathy. Kidney Int 1995; 47: 935-944.
37. Liu Z, Chen Z, Li Y. Phenotypic and functional alterations of mesangial cells in patients with diabetic nephropathy. [Chinese]. Chung Hua I Hsueh Tsa Chih 2001; 81: 1369-1373.
38. Hai CM, Murphy RA. Regulation of shortening velocity by cross-bridge phosphorylation in smooth muscle. Am J Physiol 1988; 255: C86-94.
39. Samuel M, Chowrashi PK, Pepe FA, Chacko S. Effects of phosphorylation, magnesium, and filament assembly on actin-activated ATPase of pig urinary bladder myosin. Biochemistry 1990; 29: 7124-7132.
40. Hartshorne DJ, Ito M, Erdodi F. Myosin light chain phosphatase: subunit composition, interactions and regulation. J Muscle Res Cell M 1998; 19: 325-341.
41. Somlyo AP, Kitazawa T, Himpens B, Matthijs G, Horiuti K, Kobayashi H, et al. Modulation of Ca2+-sensitivity and of the time course of contraction in smooth muscle: a major role of protein phosphatases? Adv Protein Phosph 1989; 5: 181-195.
42. Kitazawa T, Masuo M, Somlyo AP. G protein-mediated inhibition of myosin light-chain phosphatase in vascular smooth muscle. P Natl Acad Sci USA 1991; 88: 9307-9310.
43. Matsui T, Amano M, Yamamoto T, Chihara K, Nakafuku M, Ito M, et al. Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho. EMBO J 1996; 15: 2208-2216.
44. Amano M, Ito M, Kimura K, Fukata Y, Chihara K, Nakano T, et al. Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase). J Biol Chem 1996; 271: 20246-20249.
45. Kimura K, Ito M, Amano M, Chihara K, Fukata Y, Nakafuku M, et al. Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Science 1996; 273: 245-248.
46. Nakagawa O, Fujisawa K, Ishizaki T, Saito Y, Nakao K, Narumiya S. ROCK-I and ROCK-II, two isoforms of Rho-associated coiled-coil forming protein serine/threonine kinase in mice. FEBS Lett 1996; 392: 189-193.
47. Chang S, Hypolite J, Wein AJ, Chacko S, DiSanto ME. Expression of myosin light chain kinase and Rho-associated kinase in corpus cavernosum smooth muscle. Biophys J 2000; 78:139.
48. 2+ sensitization in erectile function. J Biol Chem 2002; 277: 30614-30621.
49. Rees RW, Ziessen T, Ralph DJ, Kell P, Moncada S, Cellek S. Human and rabbit cavernosal smooth muscle cells express Rho-kinase. Int J Impot Res 2002; 14: 1-7.
50. Chitaley K, Wingard CJ, Webb RC, Branam H, Stopper VS, Lewis RW, et al. Antagonism of Rho-kinase stimulates rat penile erection via a nitric oxide-independent pathway. Nat Med 2001; 7: 119-122.
51. Uehata M, Ishizaki T, Satoh H, Ono T, Kawahara T, Morishita T, et al. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature 1997; 389: 990-994.
52. Rees RW, Ralph DJ, Royle M, Moncada S, Cellek S. Y-27632, an inhibitor of Rho-kinase, antagonizes noradrenergic contractions in the rabbit and human penile corpus cavernosum. Brit J Pharmacol 2001; 133: 455-458.
53. Chang S, Hypolite J, Changolkar A, Wein AJ, Chacko S, DiSanto ME. Increased contractility of diabetic rabbit corpora smooth muscle in response to endothelin is mediated via Rho-kinase beta. Int J Impot Res 2003; 15: 53-62.
54. Nobe K, Paul RJ. Distinct pathways of Ca(2+) sensitization in porcine coronary artery: effects of Rho-related kinase and protein kinase C inhibition on force and intracellular Ca(2+). Circ Res 2001; 88: 1283-1290.
55. Bing W, Chang S, Hypolite JA, DiSanto ME, Zderic SA, Rolf L, et al. Obstruction-induced changes in urinary bladder smooth muscle contractility: a role for Rho kinase. Am J Physiol 2003; 285: F990-F997.
56. Begum N, Duddy N, Sandu O, Reinzie J, Ragolia L. Regulation of myosin-bound protein phosphatase by insulin in vascular smooth muscle cells: evaluation of the role of Rho kinase and phosphatidylinositol-3-kinase-dependent signaling pathways. Mol Endocrinol 2000; 14: 1365-1376.
57. Sandu OA, Ragolia L, Begum N. Diabetes in the Goto-Kakizaki rat is accompanied by impaired insulin-mediated myosin-bound phosphatase activation and vascular smooth muscle cell relaxation. Diabetes 2000; 49: 2178-2189.
58. Begum N, Sandu OA, Ito M, Lohmann SM, Smolenski A. Active Rho kinase (ROK-alpha) associates with insulin receptor substrate-1 and inhibits insulin signaling in vascular smooth muscle cells. J Biol Chem 2002; 277: 6214-6222.
59. 2+ sensitization of contraction in vascular smooth muscle. J Biol Chem 2000; 275: 21722-21729.
60. Sawada N, Itoh H, Yamashita J, Doi K, Inoue M, Masatsugu K, et al. cGMP-dependent protein kinase phosphorylates and inactivates RhoA. Biochem Biophys Res Commun 2001; 280: 798-805.
61. Chen H, Ikeda U, Shimpo M, Ikeda M, Minota S, Shimada K. Fluvastatin upregulates inducible nitric oxide synthase expression in cytokine-stimulated vascular smooth muscle cells. Hypertension 2000; 36: 923-928.
62. Ming XF, Viswambharan H, Barandier C, Ruffieux J, Kaibuchi K, Rusconi S, et al. Rho GTPase/Rho kinase negatively regulates endothelial nitric oxide synthase phosphorylation through the inhibition of protein kinase B/Akt in human endothelial cells. Mol Cell Biol 2002; 22: 8467-8477.
63. Takemoto M, Sun J, Hiroki J, Shimokawa H, Liao JK. Rho-kinase mediates hypoxia-induced downregulation of endothelial nitric oxide synthase. Circulation 2002; 106: 57-62.
64. Ikegaki I, Hattori T, Yamaguchi T, Sasaki Y, Satoh SI, Asano T, et al. Involvement of Rho-kinase in vascular remodeling caused by long-term inhibition of nitric oxide synthesis in rats. Eur J Pharmacol 2001; 427: 69-75.
65. Kataoka C, Egashira K, Inoue S, Takemoto M, Ni W, Koyanagi M, et al. Important role of Rho-kinase in the pathogenesis of cardiovascular inflammation and remodeling induced by long-term blockade of nitric oxide synthesis in rats. Hypertension 2002; 39: 245-250.
66. Cao Z, Hulthen UL, Allen TJ, Cooper ME. Angiotensin converting enzyme inhibition and calcium antagonism attenuate streptozotocin-diabetes-associated mesenteric vascular hypertrophy independently of their hypotensive action. J Hypertens 1998; 16: 793-799.
67. Connors BA, Bohlen HG, Evan AP. Vascular endothelium and smooth muscle remodeling accompanies hypertrophy of intestinal arterioles in streptozotocin diabetic rats. Microvasc Res 1995; 49: 340-349.
68. Wolfe L, Corbin JD, Francis SH. Characterization of a novel isozyme of cGMP-dependent protein kinase from bovine aorta. J Biol Chem 1989; 264: 7734-7741.
69. Francis SH, Woodford TA, Wolfe L, Corbin JD. Types I alpha and I beta isozymes of cGMP-dependent protein kinase: alternative mRNA splicing may produce different inhibitory domains. Sec Mess Phosphoprot 1988; 12: 301-310.
70. Orstavik S, Natarajan V, Tasken K, Jahnsen T, Sandberg M. Characterization of the human gene encoding the type I alpha and type I beta cGMP-dependent protein kinase (PRKG1). Genomics 1997; 42: 311-318.
71. Carvajal JA, Germain AM, Huidobro-Toro JP, Weiner CP. Molecular mechanism of cGMP-mediated smooth muscle relaxation. [Review] [150 refs]. J Cell Physiol 2000; 184: 409-420.
72. Schlossmann J, Feil R, Hofmann F. Signaling through NO and cGMP-dependent protein kinases. Ann Med 2003; 35: 21-27.
73. Lincoln TM, Dey N, Sellak H. Invited review: cGMP-dependent protein kinase signaling mechanisms in smooth muscle: from the regulation of tone to gene expression. J Appl Physiol 2001; 91: 1421-1430.
74. Pfeifer A, Klatt P, Massberg S, Ny L, Sausbier M, Hirneiss C, et al. Defective smooth muscle regulation in cGMP kinase I-deficient mice. EMBO J 1998; 17: 3045-3051.
75. Persson K, Pandita RK, Aszodi A, Abroad M, Pfeifer A, Fassler R, et al. Functional characteristics of urinary tract smooth muscles in mice lacking cGMP protein kinase type I. Am J Physiol 2000; 279: R1112-R1120.
76. Hedlund P, Aszodi A, Pfeifer A, Alm P, Hofmann F, Ahmad M, et al. Erectile dysfunction in cyclic GMP-dependent kinase I-deficient mice. P Natl Acad Sci USA 2000; 97: 2349-2354.
77. Chang S, Hypolite JA, Velez M, Changolkar A, Wein AJ, Chacko S, et al. Downregulation of cGMP-dependent, protein kinase-1 activity in the corpus cavernosum smooth muscle of diabetic rabbits. Am J Physiol 2004; 287: R950-R960.
78. Sullivan ME, Mumtaz FH, Dashwood MR, Thompson CS, Naseem KM, Bruckdorfer KR, et al. Enhanced relaxation of diabetic rabbit cavernosal smooth muscle in response to nitric oxide: potential relevance to erectile dysfunction. Int J Impot Res 2002; 14: 523-532.
79. Thompson CS, Mumtaz FH, Khan MA, Wallis RM, Mikhailidis DP, Morgan RJ, et al. The effect of sildenafil on corpus cavernosal smooth muscle relaxation and cyclic GMP formation in the diabetic rabbit. Eur J Pharmacol 2001; 425: 57-64.
80. Klotz T, Bloch W, Zimmermann J, Ruth P, Engelmann U, Addicks K. Soluble guanylate cyclase and cGMP-dependent protein kinase I expression in the human corpus cavernosum. Int J Impot Res 2000; 12: 157-164.
81. Wollert KC, Yurukova S, Kilic A, Begrow F, Fiedler B, Gambaryan S, et al. Increased effects of C-type natriuretic peptide on contractility and calcium regulation in murine hearts overexpressing cyclic GMP-dependent protein kinase I. Brit J Pharmacol 2003; 140: 1227-1236.
82. Sirotkin AV, Makarevich AV, Genieser HG, Kotwica J, Hetenyi L. Effect of four cGMP analogues with different mechanisms of action on hormone release by porcine ovarian granulosa cells in vitro. Exp Clin Endocr Diab 2000; 108: 214-219.
83. Eto M, Senba S, Morita F, Yazawa M. Molecular cloning of a novel phosphorylation-dependent inhibitory protein of protein phosphatase-1 (CPI17) in smooth muscle: its specific localization in smooth muscle. FEBS Lett 1997; 410: 356-360.
84. Li L, Eto M, Lee MR, Morita F, Yazawa M, Kitazawa T. Possible involvement of the novel CPI-17 protein in protein kinase C signal transduction of rabbit arterial smooth muscle. J Physiol 1998; 508: 871-881.
85. Woodsome TP, Eto M, Everett A, Brautigan DL, Kitazawa T. Expression of CPI-17 and myosin phosphatase correlates with Ca(2+) sensitivity of protein kinase C-induced contraction in rabbit smooth muscle. J Physiol 2001; 535: 553-564.
86. Eto M, Ohmori T, Suzuki M, Furuya K, Morita F. A novel protein phosphatase-1 inhibitory protein potentiated by protein kinase C. Isolation from porcine aorta media and characterization. J Biochem 1995; 118: 1104-1107.
87. Eto M, Kitazawa T, Yazawa M, Mukai H, Ono Y, Brautigan DL. Histamine-induced vasoconstriction involves phosphorylation of a specific inhibitor protein for myosin phosphatase by protein kinase C alpha and delta isoforms. J Biol Chem 2001; 276: 29072-29078.
88. Koyama M, Ito M, Feng J, Seko T, Shiraki K, Takase K, et al. Phosphorylation of CPI-17, an inhibitory phosphoprotein of smooth muscle myosin phosphatase, by Rho-kinase. FEBS Lett 2000; 475: 197-200.
89. Danthuluri NR, Deth RC. Phorbol ester-induced contraction of arterial smooth muscle and inhibition of alpha-adrenergic response. Biochem Biophys Res Commun 1984; 125: 1103-1109.
90. Rasmussen H, Forder J, Kojima I, Scriabine A. TPA-induced contraction of isolated rabbit vascular smooth muscle. Biochem Biophys Res Commun 1984; 122: 776-784.
91. Lee MW, Severson DL. Signal transduction in vascular smooth muscle: diacylglycerol second messengers and PKC action. Am J Physiol 1994; 267: C659-C678.
92. Singer HA, Schworer CM, Sweeley C, Benscoter H. Activation of protein kinase C isozymes by contractile stimuli in arterial smooth muscle. Arch Biochem Biophys 1992; 299: 320-329.
93. Haller H, Smallwood JI, Rasmussen H. Protein kinase C translocation in intact vascular smooth muscle strips. Biochem J 1990; 270: 375-381.
94. Housey GM, O'Brian CA, Johnson MD, Kirschmeier P, Weinstein IB. Isolation of cDNA clones encoding protein kinase C: evidence for a protein kinase C-related gene family. P Natl Acad Sci USA 1987; 84: 1065-1069.
95. Idris I, Gray S, Donnelly R. Protein kinase C activation: isozyme-specific effects on metabolism and cardiovascular complications in diabetes. Diabetologia 2001; 44: 659-673.
96. Newton AC. Protein kinase C: structure, function, and regulation. J Biol Chem 1995; 270: 28495-28498.
97. Bengur AR, Robinson EA, Appella E, Sellers JR. Sequence of the sites phosphorylated by protein kinase C in the smooth muscle myosin light chain. J Biol Chem 1987; 262: 7613-7617.
98. Ikebe M, Hartshorne DJ, Elzinga M. Phosphorylation of the 20, 000-dalton light chain of smooth muscle myosin by the calcium-activated, phospholipid-dependent protein kinase. Phosphorylation sites and effects of phosphorylation. J Biol Chem 1987; 262: 9569-9573.
99. Clark T, Ngai PK, Sutherland C, Groschel-Stewart U, Walsh MP. Vascular smooth muscle caldesmon. J Biol Chem 1986; 261: 8028-8035.
100. Takahashi K, Hiwada K, Kokubu T. Vascular smooth muscle calponin. A novel troponin T-like protein. Hypertension 1988; 11: 620-626.
101. Winder SJ, Walsh MP. Smooth muscle calponin. Inhibition of actomyosin MgATPase and regulation by phosphorylation. J Biol Chem 1990; 265: 10148-10155.
102. Ngai PK, Walsh MP. The effects of phosphorylation of smooth-muscle caldesmon. Biochem J 1987; 244: 417-425.
103. Okamoto K, Kashihara N, Yamasaki Y, Kanao K, Maeshima Y, Sekikawa T, et al. Caldesmon isoform associated with phenotypic modulation of mesangial cells. Exp Nephrol 2000; 8: 20-27.
104. Murphy M, Godson C, Cannon S, Kato S, Mackenzie HS, Martin F, et al. Suppression subtractive hybridization identifies high glucose levels as a stimulus for expression of connective tissue growth factor and other genes in human mesangial cells. J Biol Chem 1999; 274: 5830-5834.
105. Makino H, Kashihara N, Sugiyama H, Kanao K, Sekikawa T, Shikata K, et al. Phenotypic changes of the mesangium in diabetic nephropathy. J Diabetes Complicat 1995; 9: 282-284.
106. Mao Y, Ootaka T, Saito T, Sato H, Sato T, Ito S. The involvement of advanced glycation endproducts (AGEs) in renal injury of diabetic glomerulosclerosis: association with phenotypic change in renal cells and infiltration of immune cells. Clin Exp Nephrol 2003; 7: 201-209.
107. Natarajan R, Gonzales N, Xu L, Nadler JL. Vascular smooth muscle cells exhibit increased growth in response to elevated glucose. Biochem Biophys Res Commun 1992; 187: 552-560.
108. Inoguchi T, Battan R, Handler E, Sportsman JR, Heath W, King GL. Preferential elevation of protein kinase C isoform beta II and diacylglycerol levels in the aorta and heart of diabetic rats: differential reversibility to glycemic control by islet cell transplantation. Proc Natl Acad Sci USA 1992; 89: 11059-11063.
109. Lagaud GJ, Masih-Khan E, Kai S, van Breemen C, Dube GP. Influence of type II diabetes on arterial tone and endothelial function in murine mesenteric resistance arteries. J Vasc Res 2001; 38: 578-589.
110. Nakamura J, Kasuya Y, Hamada Y, Nakashima E, Naruse K, Yasuda Y, et al. Glucose-induced hyperproliferation of cultured rat aortic smooth muscle cells through polyol pathway hyperactivity. Diabetologia 2001; 44: 480-487.
111. Ganz MB, Seftel A. Glucose-induced changes in protein kinase C and nitric oxide are prevented by vitamin E. Am J Physiol 2000; 278: E146-E152.
112. Husain S, Young D, Wingard CJ. Role of PKCα and PKCι in phenylephrine-induced contraction of rat corpora cavernosa. Int J Impot Res 2004; 16: 325-333.
113. Shaw S, Wang X, Redd H, Alexander GD, Isales CM, Marrero MB. High glucose augments the angiotensin II-induced activation of JAK2 in vascular smooth muscle cells via the polyol pathway. J Biol Chem 2003; 278: 30634-30641.
114. Ishii H, Jirousek MR, Koya D, Takagi C, Xia P, Clermont A, et al. Amelioration of vascular dysfunctions in diabetic rats by an oral PKC beta inhibitor. Science 1996; 272: 728-731.
115. Koya D, Haneda M, Nakagawa H, Isshiki K, Sato H, Maeda S, et al. Amelioration of accelerated diabetic mesangial expansion by treatment with a PKC beta inhibitor in diabetic db/db mice, a rodent model for type 2 diabetes. FASEB J 2000; 14: 439-447.
116. Kelly DJ, Zhang Y, Hepper C, Gow RM, Jaworski K, Kemp BE, et al. Protein kinase C beta inhibition attenuates the progression of experimental diabetic nephropathy in the presence of continued hypertension. Diabetes 2003; 52: 512-518.
117. Haneda M, Koya D, Kikkawa R. Cellular mechanisms in the development and progression of diabetic nephropathy: activation of the DAG-PKC-ERK pathway. Am J Kidney Dis 2001; 38: S178-S181.
118. Cotter MA, Jack AM, Cameron NE. Effects of the protein kinase C beta inhibitor LY333531 on neural and vascular function in rats with streptozotocin-induced diabetes. Clin Sci 2002; 103: 311-321.
119. Nangle MR, Cotter MA, Cameron NE. Protein kinase C beta inhibition and aorta and corpus cavernosum function in streptozotocin-diabetic mice. Eur J Pharmacol 2003; 475: 99-106.
120. 2+-independent smooth muscle contraction. a novel function for integrin-linked kinase. J Biol Chem 2001; 276: 16365-16373.
121. Deng JT, Sutherland C, Brautigan DL, Eto M, Walsh MP. Phosphorylation of the myosin phosphatase inhibitors, CPI-17 and PHI-1, by integrin-linked kinase. Biochem J 2002; 367: 517-524.
122. MacDonald JA, Borman MA, Muranyi A, Somlyo AV, Hartshorne DJ, Haystead TA. Identification of the endogenous smooth muscle myosin phosphatase-associated kinase. Proc Natl Acad Sci USA 2001; 98: 2419-2424.
123. Niiro N, Ikebe M. Zipper-interacting protein kinase induces Ca(2+)-free smooth muscle contraction via myosin light chain phosphorylation. J Biol Chem 2001; 276: 29567-29574.
124. 2+ sensitization via myosin phosphatase inhibition. J Biol Chem 2002; 277: 23441-23446.
125. MacDonald JA, Eto M, Borman MA, Brautigan DL, Haystead TA. Dual Ser and Thr phosphorylation of CPI-17, an inhibitor of myosin phosphatase, by MYPT-associated kinase. FEBS Lett 2001; 493: 91-94.
126. Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988; 332: 411-415.
127. Luscher TF, Barton M. Endothelins and endothelin receptor antagonists: therapeutic considerations for a novel class of cardiovascular drugs. Circulation 2000; 102: 2434-2440.
128. Usuki S, Kondoh K, Kubo T. Plasma endothelin and LH-RH, LH, FSH, prolactin, progesterone, 17alpha-hydroxyprogesterone, estrone, 17beta-estradiol, delta4-androstenedione, testosterone, active renin, angiotensin-II and ANP levels in blood and LH, estrone and 17beta-estradiol and pregnanediol levels in urine of normal cycling women. J Cardiovasc Pharm 2000; 36: S421-S427.
129. Saenz de TI, Carson MP, de las MA, Goldstein I, Traish AM. Endothelin: localization, synthesis, activity, and receptor types in human penile corpus cavernosum. Am J Physiol 1991; 261: H1078-H1085.
130. Filippi S, Luconi M, Granchi S, Natali A, Tozzi P, Forti G, et al. Endothelium-dependency of yohimbine-induced corpus cavernosum relaxation. Int J Impot Res 2002; 14: 295-307.
131. Makino A, Kamata K. Time-course changes in plasma endothelin-1 and its effects on the mesenteric arterial bed in streptozotocin-induced diabetic rats. Diabetes Obes Metab 2000; 2: 47-55.
132. Takeda Y, Miyamori I, Yoneda T, Takeda R. Production of endothelin-1 from the mesenteric arteries of streptozotocin-induced diabetic rats. Life Sci 1991; 48: 2553-2556.
133. Schneider JG, Tilly N, Hierl T, Sommer U, Hamann A, Dugi K, et al. Elevated plasma endothelin-1 levels in diabetes mellitus. Am J Hypertens 2002; 15: 967-972.
134. Ak G, Buyukberber S, Sevinc A, Turk HM, Ates M, Sari R, et al. The relation between plasma endothelin-1 levels and metabolic control, risk factors, treatment modalities, and diabetic microangiopathy in patients with Type 2 diabetes mellitus. J Diabetes Complicat 2001; 15: 150-157.
135. Migdalis IN, Kalogeropoulou K, Iiopoulou V, Varvarigos N, Karmaniolas KD, Mortzos G, et al. Progression of carotid atherosclerosis and the role of endothelin in diabetic patients. Res Commun Mol Path 2000; 108: 27-37.
136. Sarman B, Farkas K, Toth M, Somogyi A, Tulassay Z. Circulating plasma endothelin-1, plasma lipids and complications in Type 1 diabetes mellitus. Diabetes Nutr Metab - Clin Exp 2000; 13: 142-148.
137. Sakamoto A, Yanagisawa M, Sakurai T, Takuwa Y, Yanagisawa H, Masaki T. Cloning and functional expression of human cDNA for the ETB endothelin receptor. Biochem Biophys Res Commun 1991; 178: 656-663.
138. Nakamuta M, Takayanagi R, Sakai Y, Sakamoto S, Hagiwara H, Mizuno T, et al. Cloning and sequence analysis of a cDNA encoding human non-selective type of endothelin receptor. Biochem Biophys Res Commun 1991; 177: 34-39.
139. Matsuda H, Beppu S, Ohmori F, Yamada M, Miyatake K. Involvement of cyclo-oxygenase-generated vasodilating eicosanoid(s) in addition to nitric oxide in endothelin-1-induced endothelium-dependent vasorelaxation in guinea pig aorta. Heart Vessels 1993; 8: 121-127.
140. Sumner MJ, Cannon TR, Mundin JW, White DG, Watts IS. Endothelin ETA and ETB receptors mediate vascular smooth muscle contraction. Brit J Pharmacol 1992; 107: 858-860.
141. Bell CR, Sullivan ME, Dashwood MR, Muddle JR, Morgan RJ. The density and distribution of endothelin 1 and endothelin receptor subtypes in normal and diabetic rat corpus cavernosum. Br J Urol 1995; 76: 203-207.
142. Christ GJ, Lerner SE, Kim DC, Melman A. Endothelin-1 as a putative modulator of erectile dysfunction: I. Characteristics of contraction of isolated corporal tissue strips. J Urol 1995; 153: 1998-2003.
143. Nakamura I, Saito M, Fukumoto Y, Yoshida M, Nishi K, Weiss RM, et al. Experimental diabetes upregulates the expression of uretereral endothelin receptors. Peptides 1997; 18: 1091-1093.
144. Mumtaz FH, Dashwood MR, Thompson CS, Sullivan ME, Mikhailidis DP, Morgan RJ. Increased expression of endothelin B receptors in the diabetic rabbit urinary bladder: functional relevance. BJU Int 1999; 83: 113-122.
145. Saito M, Nishi K, Fukumoto Y, Weiss RM, Latifpour J. Characterization of endothelin receptors in streptozotocin-induced diabetic rat vas deferens. Biochem Pharmacol 1996; 52: 1593-1598.
146. Saito M, Nishi K, Foster HE Jr, Weiss RM, Latifpour J. Effect of experimental diabetes on rat prostate endothelin receptors. Eur J Pharmacol 1996; 310: 197-200.
147. Sullivan ME, Dashwood MR, Thompson CS, Muddle JR, Mikhailidis DP, Morgan RJ. Alterations in endothelin B receptor sites in cavernosal tissue of diabetic rabbits: potential relevance to the pathogenesis of erectile dysfunction. J Urol 1997; 158: 1966-1972.
148. Khan MA, Calvert RC, Sullivan ME, Thompson CS, Mumtaz FH, Morgan RJ, et al. Normal and pathological erectile function: the potential clinical role of endothelin-1 antagonists. Curr Drug Targets 2000; 1: 247-260.
149. Kim NN, Dhir V, Azadzoi KM, Traish AM, Flaherty E, Goldstein I. Pilot study of the endothelin-A receptor selective antagonist BMS-193884 for the treatment of erectile dysfunction. J Androl 2002; 23: 76-83.
150. Yang D, Bivalacqua TJ, Hyun J, Leungwattanakij S, Sikka SC, Baig M, et al. The role of endothelin antagonism for the preservation of erectile function in diabetic rats. J Urol 2001; 165: 230.
151. Rich S, McLaughlin VV. Endothelin receptor blockers in cardiovascular disease. Circulation 2003; 108: 2184-2190.
152. Hedlund H, Andersson KE. Contraction and relaxation induced by some prostanoids in isolated human penile erectile tissue and cavernous artery. J Urol 1985; 134: 1245-1250.
153. Angulo J, Cuevas P, La Fuente JM, Pomerol JM, Ruiz-Castane E, Puigvert A, et al. Regulation of human penile smooth muscle tone by prostanoid receptors. Brit J Pharmacol 2002; 136: 23-30.
154. Hedlund H, Andersson KE, Fovaeus M, Holmquist F, Uski T. Characterization of contraction-mediating prostanoid receptors in human penile erectile tissues. J Urol 1989; 141: 182-186.
155. Talubmook C, Forrest A, Parsons M. Streptozotocin-induced diabetes modulates presynaptic and postsynaptic function in the rat ileum. Eur J Pharmacol 2003; 469: 153-158.
156. Oliveira MA, Carvalho MH, Nigro D, Passaglia RC, Fortes ZB. Elevated glucose blocks angiotensin-(1-7) and bradykinin interaction: the role of cyclooxygenase products. Peptides 2003; 24: 449-454.
157. Hoeldtke RD, Bryner KD, McNeill DR, Warehime SS, Van Dyke K, Hobbs G. Oxidative stress and insulin requirements in patients with recent-onset type 1 diabetes. J Clin Endocr Metab 2003; 88: 1624-1628.
158. Adam LP, Hathaway DR. Identification of mitogen-activated protein kinase phosphorylation sequences in mammalian h-Caldesmon. FEBS Lett 1993; 322: 56-60.
159. Gerthoffer WT, Yamboliev IA, Pohl J, Haynes R, Dang S, McHugh J. Activation of MAP kinases in airway smooth muscle. Am J Physiol 1997; 272: L244-L252.
160. D'Angelo G, Graceffa P, Wang CA, Wrangle J, Adam LP. Mammal-specific, ERK-dependent, caldesmon phosphorylation in smooth muscle. Quantitation using novel anti-phosphopeptide antibodies. J Biol Chem 1999; 274: 30115-30121.
161. Gerthoffer WT, Yamboliev IA, Shearer M, Pohl J, Haynes R, Dang S, et al. Activation of MAP kinases and phosphorylation of caldesmon in canine colonic smooth muscle. J Physiol 1996; 495: 597-609.
162. Je HD, Gangopadhyay SS, Ashworth TD, Morgan KG. Calponin is required for agonist-induced signal transduction--evidence from an antisense approach in ferret smooth muscle. J Physiol 2001; 537: 567-577.
163. Yamboliev IA, Hedges JC, Mutnick JL, Adam LP, Gerthoffer WT. Evidence for modulation of smooth muscle force by the p38 MAP kinase/HSP27 pathway. Am J Physiol 2000; 278: H1899-H1907.
164. Meloche S, Landry J, Huot J, Houle F, Marceau F, Giasson E. p38 MAP kinase pathway regulates angiotensin II-induced contraction of rat vascular smooth muscle. Am J Physiol 2000; 279: H741-H751.
165. Natarajan R, Scott S, Bai W, Yerneni KK, Nadler J. Angiotensin II signaling in vascular smooth muscle cells under high glucose conditions. Hypertension 1999; 33: 378-384.
166. Igarashi M, Wakasaki H, Takahara N, Ishii H, Jiang ZY, Yamauchi T, et al. Glucose or diabetes activates p38 mitogen-activated protein kinase via different pathways. J Clin Invest 1999; 103: 185-195.
167. Touyz RM, Schiffrin EL. Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin II in vascular smooth muscle cells. Pharmacol Rev 2000; 52: 639-672.
168. Park JK, Kim SZ, Kim SH, Park YK, Cho KW. Renin angiotensin system in rabbit corpus cavernosum: functional characterization of angiotensin II receptors. J Urol 1997; 158: 653-658.
169. Kifor I, Williams GH, Vickers MA, Sullivan MP, Jodbert P, Dluhy RG. Tissue angiotensin II as a modulator of erectile function. I. Angiotensin peptide content, secretion and effects in the corpus cavernosum. J Urol 1997; 157: 1920-1925.
170. Becker AJ, Uckert S, Stief CG, Truss MC, Machtens S, Scheller F, et al. Possible role of bradykinin and angiotensin II in the regulation of penile erection and detumescence. Urol 2001; 57: 193-198.
171. Becker AJ, Uckert S, Stief CG, Scheller F, Knapp WH, Hartmann U, et al. Plasma levels of angiotensin II during different penile conditions in the cavernous and systemic blood of healthy men and patients with erectile dysfunction. Urology 2001; 58: 805-810.
172. Head RJ, Longhurst PA, Panek RL, Stitzel RE. A contrasting effect of the diabetic state upon the contractile responses of aortic preparations from the rat and rabbit. Brit J Pharmacol 1987; 91: 275-286.
173. McNally PG, Watt PA, Rimmer T, Burden AC, Hearnshaw JR, Thurston H. Impaired contraction and endothelium-dependent relaxation in isolated resistance vessels from patients with insulin-dependent diabetes mellitus. Clin Sci 1994; 87: 31-36.
174. Fujita N, Furukawa Y, Du J, Itabashi N, Fujisawa G, Okada K, et al. Hyperglycemia enhances VSMC proliferation with NF-kappaB activation by angiotensin II and E2F-1 augmentation by growth factors. Mol Cell Endocrinol 2002; 192: 75-84.
175. Wiener J, Lombardi DM, Su JE, Schwartz SM. Immunohistochemical and molecular characterization of the differential response of the rat mesenteric microvasculature to angiotensin-II infusion. J Vasc Res 1996; 33: 195-208.
176. Natarajan R, Gonzales N, Lanting L, Nadler J. Role of the lipoxygenase pathway in angiotensin II-induced vascular smooth muscle cell hypertrophy. Hypertension 1994; 23: I142-I147.
177. Andersson KE. Pharmacology of penile erection. Pharmacol Rev 2001; 53: 417-450.
178. Levin RM, Wein AJ. Adrenergic alpha receptors outnumber beta receptors in human penile corpus cavernosum. Invest Urol 1980; 18: 225-226.
179. Mills TM, Lewis RW, Stopper VS, Reilly CM. The loss of alpha-adrenergic effect during the erectile response in the long-term diabetic rat. J Androl 1998; 19: 473-478.
180. Takahashi T, Kojima Y, Tsunoda Y, Beyer LA, Kamijo M, Sima AA, et al. Impaired intracellular signal transduction in gastric smooth muscle of diabetic BB/W rats. Am J Physiol 1996; 270: G411-G417.
181. Sharma K, Wang L, Zhu Y, DeGuzman A, Cao GY, Lynn RB, et al. Renal type I inositol 1, 4, 5-trisphosphate receptor is reduced in streptozotocin-induced diabetic rats and mice. Am J Physiol 1999; 276: F54-F61.
182. Herrero MB, de Lamirande E, Gagnon C. Nitric oxide is a signaling molecule in spermatozoa. Curr Pharm Design 2003; 9(5): 419-25.
183. McCann SM, Haens G, Mastronardi C, Walczewska A, Karanth S, Rettori V, et al. The role of nitric oxide (NO) in control of LHRH release that mediates gonadotropin release and sexual behavior. Curr Pharm Design 2003; 9(5): 381-90.
184. Weber T, Auer J, Eisserer G, Berent R, Eber B, O'Rourke MF. Arterial stiffness and cardiovascular drugs. Curr Pharm Design 2003; 9(13): 1049-63.