Physiological significance and therapeutic potential of adrenomedullin in pulmonary hypertension

Cardiovascular and Hematological Disorders - Drug Targets

Volumn 6, Issue 2, 2006, Pages 123-130

  Murakami, Shinsuke ^a,b   Kimura, Hiroshi ^b   Kangawa, Kenji ^a   Nagaya, Noritoshi ^a  

^a NATIONAL CEREBRAL AND CARDIOVASCULAR CENTER   (Japan)

^b NARA MEDICAL UNIVERSITY   (Japan)

Author keywords

5 monophosphate; Adrenomedullin; Akt; Angiogenesis; Anti apoptosis; Cyclic adenosine 3 ; Endothelial progenitor cell; Gene therapy; Nitric oxide; Pulmonary hypertension; Vasodilation

Indexed keywords

ADRENOMEDULLIN; ADRENOMEDULLIN RECEPTOR; CYCLIC AMP; ILOPROST; MITOGEN ACTIVATED PROTEIN KINASE; MONOCROTALINE; NITRIC OXIDE; PEPTIDE; PROSTACYCLIN; PROSTACYCLIN DERIVATIVE; PROTEIN KINASE B; VASODILATOR AGENT;

ANGIOGENESIS; APOPTOSIS; BLOOD VESSEL; DISEASE SEVERITY; DRUG ACTIVITY; ENDOTHELIUM; ENZYME ACTIVATION; HEART; HUMAN; LUNG; LUNG ARTERY PRESSURE; LUNG VASCULAR RESISTANCE; NONHUMAN; PROTEIN BLOOD LEVEL; PROTEIN LOCALIZATION; PROTEIN METABOLISM; PULMONARY HYPERTENSION; REGULATORY MECHANISM; REVIEW; STEM CELL; VASODILATATION;

EID: 33744794069     PISSN: 1871529X     EISSN: None     Source Type: Journal    
DOI: 10.2174/187152906777441867     Document Type: Review

References (107)

1. Rich, S., Dantzker, D.R., Ayres, S.M., Bergofsky, E.H., Brundage, B.H., Detre, K.M., Fishman, A.P., Goldring, R.M., Groves, B.M., Koerner, S.K. Primary pulmonary hypertension. A national prospective study. Ann. Intern. Med., 1987, 107, 216-223.
2. D'Alonzo, G.E., Barst, R.J., Ayres, S.M., Bergofsky, E.H., Brundage, B.H., Detre, K.M., Fishman, A.P., Goldring, R.M., Groves, B.M., Kernis, J.T. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann. Intern Med., 1991, 115, 343-349.
3. Archer, S., Rich, S. Primary pulmonary hypertension: a vascular biology and translational research "Work in progress". Circulation, 2000, 102, 2781-2791.
4. Barst, R.J., Rubin, L.J., Long, W.A, McGoon, M.D., Rich, S., Badesch, D.B., Groves, B.M., Tapson, V.F., Bourge, R.C., Brundage, B.H. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. The Primary Pulmonary Hypertension Study Group. N. Engl. J. Med., 1996, 334, 296-302.
5. McLaughlin, V.V., Genthner, D.E., Panella, M.M., Rich, S. Reduction in pulmonary vascular resistance with long-term epoprostenol (prostacyclin) therapy in primary pulmonary hypertension. N. Engl. J. Med., 1998, 338, 273-277.
6. Rubin, L.J., Mendoza, J., Hood, M., McGoon, M., Barst, R., Williams, W.B., Diehl, J.H., Crow, J., Long, W. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Results of a randomized trial. Ann. Intern. Med., 1990, 112, 485-491.
7. Reitz, B.A., Wallwork, J.L., Hunt, S.A., Pennock, J.L., Billingham, M.E., Oyer, P.E., Stinson, E.B., Shumway, N.E. Heart-lung transplantation: successful therapy for patients with pulmonary vascular disease. N. Engl. J. Med., 1982, 306, 57-64.
8. Pasque, M.K., Trulock, E.P., Kaiser, L.R. Cooper, J.D. Single-lung transplantation for pulmonary hypertension. Three-month hemodynamic follow-up. Circulation, 1991, 84, 2275-2279.
9. Kitamura, K., Kangawa, K., Kawamoto, M., Ichiki, Y., Nakamura, S., Matsuo, H., Eto, T. Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem. Biophys. Res. Commun., 1993, 192, 553-560.
10. McLatchie, L.M., Fraser, N.J., Main, M.J., Wise, A., Brown, J., Thompson, N., Solari, R., Lee, M.G., Foord, S.M. RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature, 1998, 393, 333-339.
11. Ichiki, Y., Kitamura, K., Kangawa, K., Kawamoto, M., Matsuo, H., Eto, T. Distribution and characterization of immunoreactive adrenomedullin in human tissue and plasma. FEBS Lett., 1994, 338, 6-10.
12. Sakata, J., Shimokubo, T., Kitamura, K., Nishizono, M., Iehiki, Y., Kangawa, K., Matsuo, H., Eto, T. Distribution and characterization of immunoreactive rat adrenomedullin in tissue and plasma. FEBS Lett., 1994, 352, 105-108.
13. 2+ mobilization, in bovine aortic endothelial cells. J. Biol. Chem., 1995, 270, 4412-4417.
14. Sugo, S., Minamino, N., Kangawa, K., Miyamoto, K., Kitamura, K., Sakata, J., Eto, T., Matsuo, H. Endothelial cells actively synthesize and secrete adrenomedullin. Biochem Biophys. Res. Commun., 1994, 201, 1160-1166.
15. Sugo, S., Minamino, N., Shoji, H., Kangawa, K., Kitamura, K., Eto, T., Marano, H. Production and secretion of adrenomedullin from vascular smooth muscle cells: augmented production by tumor necrosis factor-alpha. Biochem. Biophys. Res. Commun., 1994, 203, 719-726.
16. Majid, D.S., Kadowitz, P.J., Coy, D.H., Navar, L.G. Renal responses to intra-arterial administration of adrenomedullin in dogs. Am. J. Physiol., 1996, 270, F200-F205.
17. Parkes, D.G., May, C.N. Direct cardiac and vascular actions of adrenomedullin in conscious sheep. Br. J. Pharmacol., 1997, 120, 1179-1185.
18. Szokodi, I., Kinnunen, P., Tavi, P., Weckstrom, M., Toth, M., Ruskoaho, H. Evidence for cAMP-independent mechanisms mediating the effects of adrenomedullin, a new inotropic peptide. Circulation, 1998, 97, 1062-70.
19. Nagaya, N., Goto, Y., Satoh, T., Sumida, H., Kojima, S., Miyatake, K., Kangawa, K. Intravenous adrenomedullin in myocardial function and energy metabolism in patients after myocardial infarction. J. Cardiovasc. Pharmacol., 2002, 39, 754-760.
20. Kato, H., Shichiri, M., Matumo, F., Hirata, Y. Adrenomedullin as an autocrine/paracrine apoptosis survival factor for rat endothelial cells. Endocrinology, 1997, 138, 2615-2620.
21. Nagaya, N., Mori, H., Murakami, S., Kangawa, K., Kitamura, S. Adrenomedullin: angiogenesis and gene therapy. Am. J. Physiol. Regul. Integr. Comp. Physiol., (in press).
22. Hanabusa, K., Nagaya, N., Iwase, T., Itoh, T., Murakami, S., Shimizu, Y., Taki, W., Miyatake, K., Kangawa, K. Adrenomedullin enhances therapeutic potency of mesenchymal stem cells after experimental stroke in rats. Stroke. 2005, 36, 853-858.
23. Iwase, T., Nagaya, N., Fujii, T., Itoh, T., Ishibashi-Ueda, H., Yamagishi, M., Miyatake, K., Matsumoto, T., Kitamura, S., Kangawa, K. Adrenomedullin enhances angiogenic potency of bone marrow transplantation in a rat model of hindlimb ischemia. Circulation, 2005, 111, 356-362.
24. Fujii, T., Nagaya, N., Iwase, T., Murakami, S., Miyahara, Y., Nishigami, K., Ishibashi-Ueda H., Shirai, M., Itoh, T., Ishino, K., Sano, S., Kangawa, K., Mori, H. Adrenomedullin enhances therapeutic potency of bone marrow transplantation for myocardial infarction in rats. Am. J. Physiol. Heart. Circ. Physiol., 2005, 288, H1444-H1450.
25. Okumura, H., Nagaya, N., Itoh, T., Okano, I., Hino, J., Mori, K., Tsukamoto, Y., Ishibashi-Ueda, H., Miwa, S., Tambara, K., Toyokuni, S., Yutani, C., Kangawa, K. Adrenomedullin infusion attenuates myocardial ischemia/reperfusion injury through the phosphatidylinositol 3-kinase/ Akt-dependent pathway. Circulation, 2004, 109, 242-248.
26. Kohno, M., Hanehira, T., Kano, H., Horio, T., Yokokawa, K., Ikeda, M., Minami, M., Yasunari, K., Yoshikawa, J. Plasma adrenomedullin concentrations in essential hypertension. Hypertension, 1996, 27, 102-107.
27. Nishikimi, T., Yoshihara, F., Kanazawa, A., Okano, I., Horio, T., Nagaya, N., Yutani, C., Matsuo, H., Matsuoka, H., Kangawa, K. Role of increased circulating and renal adrenomedullin in rats with malignant hypertension. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2001, 281, R2079-R2087.
28. Nishikimi, T., Horio, T., Kohmoto, Y., Yoshihara, F., Nagaya, N., Inenaga, T., Saito, M., Teranishi, M., Nakamura, M., Ohrui, M., Kawano, Y., Matsuo, H., Ishimitsu, T., Takishita, S., Matsuoka, H., Kangawa, K. Molecular forms of plasma and urinary adrenomedullin in normal, essential hypertension and chronic renal failure. J. Hypertens., 2001, 19, 765-773.
29. Kobayashi, K., Kitamura, K., Hirayama, N., Date, H., Kashiwagi, T., Ikushima, I., Hanada, Y., Nagatomo, Y., Takenaga, M., Ishikawa, T., Imamura, T., Koiwaya, Y., Eto, T. Increased plasma adrenomedullin in acute myocardial infarction. Am. Heart J., 1996, 131, 676-680.
30. Miyao, Y., Nishikimi, T., Goto, Y., Miyazaki, S., Daikoku, S., Morii, I., Matsumoto, T., Takishita, S., Miyata, A., Matsuo, H., Kangawa, K., Nonogi, H. Increased plasma adrenomedullin levels in patients with acute myocardial infarction in proportion to the clinical severity. Heat, 1998, 79, 39-44.
31. Nagaya, N., Nishikimi, T., Yoshihara, F., Horio, T., Morimoto, A., Kangawa, K. Cardiac adrenomedullin gene expression and peptide accumulation after acute myocardial infarction in rats. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2000, 278, R1019-R1026.
32. Nagaya, N., Nishikimi, T., Uematsu, M., Yoshitomi, Y., Miyao, Y., Miyazaki, S., Goto, Y., Kojima, S., Kuramochi, M., Matsuo, H., Kangawa, K., Nonogi, H. Plasma adrenomedullin as an indicator of prognosis after acute myocardial infarction. Heart, 1999, 81, 483-487.
33. Jougasaki, M., Wei, C.M., McKinley, L.J., Burnett, J.C.Jr., Elevation of circulating and ventricular adrenomedullin in human congestive heart failure. Circulation, 1995, 92, 286-289.
34. Nishikimi, T., Saito, Y., Kitamura, K., Ishimitsu, T., Eto, T., Kangawa, K., Matsuo, H., Omae, T., Matsuoka, H. Increased plasma levels of adrenomedullin in patients with heart failure. J. Am. Coll. Cardiol., 1995, 26, 1424-1431.
35. Watanabe, K., Nishikimi, T., Takamuro, M., Yasuda, K., Ishikawa, Y., Tanabe, S., Yamada, O., Nagaya, N., Matsuoka, H., Kangawa, K., Echigo, S. Two molecular forms of adrenomedullin in congenital heart disease. Pediatr. Cardiol., 2003, 24, 559-565.
36. Tambara, K., Fujita, M., Nagaya, N., Miyamoto, S., Iwakura, A., Doi, K., Sakaguchi, G., Nishimura, K., Kangawa, K., Komeda, M. Increased pericardial fluid concentrations of the mature form of adrenomedullin in patients with cardiac remodelling. Heart, 2002, 87, 242-246.
37. Yoshihara, F., Nishikimi, T., Horio, T., Yutani, C., Nagaya N., Matsuo, H., Ohe, T., Kangawa, K. Ventricular adrenomedullin concentration is a sensitive biochemical marker for volume and pressure overload in rats. Am. J. Physiol. Heart. Circ. Physiol., 2000, 278, H633-H642.
38. Morimoto, A., Nishikimi, T., Yoshihara, F., Horio, T., Nagaya, N., Matsuo, H., Dohi, K., Kangawa, K. Ventricular adrenomedullin levels correlate with the extent of cardiac hypertrophy in rats. Hypertension, 1999, 33, 1146-1152.
39. Nagaya, N., Nishikimi, T., Horio, T., Yoshihara, F., Kanazawa, A., Matsuo, H., Kangawa, K. Cardiovascular and renal effects of adrenomedullin in rats with heart failure. Am. J. Physiol., 1999, 276, R213-R218.
40. Ishimitsu, T., Nishikimi, T., Saito, Y., Kitamura, K., Eto, T., Kangawa, K., Matsuo, H., Omae, T., Matsuoka, H. Plasma levels of adrenomedullin, a newly identified hypotensive peptide, in patients with hypertension and renal failure. J. Clin. Invest., 1994, 94, 2158-2161.
41. Kakishita, M., Nishikimi, T., Okano, Y., Satoh, T., Kyotani, S., Nagaya, N., Fukushima, K., Nakanishi, N., Takishita, S., Miyata, A., Kangawa, K., Matsuo, H., Kunieda, T. Increased plasma levels of adrenomedullin in patients with pulmonary hypertension. Clin. Sci., (Lond) 1999, 96, 33-39.
42. Vijay, P., Szekely, L., Sharp, T.G., Miller, A., Bando, K., Brown, J.W. Adrenomedullin in patients at high risk for pulmonary hypertension. Ann. Thorac. Surg., 1998, 66, 500-505.
43. Nishikimi, T., Nagata, S., Sasaki, T., Yoshihara, F., Nagaya, N., Horio, T., Matsuo, H., Matsuoka, H., Kangawa, K. The active molecular form of plasma adrenomedullin is extracted in the pulmonary circulation in patients with mitral stenosis: possible role of adrenomedullin in pulmonary hypertension. Clin. Sci (Lond)., 2001, 100, 61-66.
44. Shimosawa, T., Shibagaki, Y., Ishibashi, K., Kitamura, K., Kangawa, K., Kato, S., Ando, K., Fujita, T. Adrenomedullin, an endogenous peptide, counteracts cardiovascular damage. Circulation, 2002, 105, 106-111.
45. Niu, P., Shindo, T., Iwata, H., Iimuro, S., Takeda, N., Zhang, Y., Ebihara, A., Suematsu, Y., Kangawa, K., Hirata, Y., Nagai, R. Protective effects of endogenous adrenomedullin on cardiac hypertrophy, fibrosis, and renal damage. Circulation, 2004, 109, 1789-1794.
46. Yoshibayashi, M., Kamiya, T., Kitamura, K., Saito, Y., Kangawa, K., Nishikimi, T., Matsuoka, H., Eto, T., Matsuo, H. Plasma levels of adrenomedullin in primary and secondary pulmonary hypertension in patients <20 years of age. Am. J. Cardiol., 1997, 79, 1556-1558.
47. Shimokubo, T., Sakata, J., Kitamura, K., Kangawa, K., Matsou, H., Eto, T. Augmented adrenomedullin concentrations in right ventricle and plasma of experimental pulmonary hypertension. Life Sci., 1995, 57, 1771-1779.
48. Kitamura, K., Sakata, J., Kangawa, K., Kojima, M., Matsuo, H., Eto, T. Cloning and characterization of cDNA encoding a precursor for human adrenomedullin. Biochem. Biophys. Res. Commun., 1993, 194, 720-725.
49. Nishikimi, T., Kitamura, K., Saito, Y., Shimada, K., Ishimitsu, T., Takamiya, M., Kangawa, K., Matsuo, H., Eto, T., Omae, T. Clinical studies on the sites of production and clearance of circulating adrenomedullin in human subjects. Hypertensiopt 1994, 24, 600-604.
50. Nakayama, M., Takahashi, K., Murakami, O., Shirato, K., Shibahara, S. Induction of adrenomedullin by hypoxia and cobalt chloride in human colorectal carcinoma cells. Biochem. Biophys. Res. Commun., 1998, 243, 514-517.
51. Sugo, S., Minamino, N., Shoji, H., Kangawa, K., Kitamura, K., Eto, T., Matsuo, H. Interleukin-1, tumor necrosis factor and lipopolysaccharide additively stimulate production of adrenomedullin in vascular smooth muscle cells. Biochem. Biophys. Res. Commun., 1995, 207, 25-32.
52. Chun, T.H., Rob, H., Ogawa, Y., Tamura, N., Takaya, K., Igaki, T., Yamashita, J., Doi, K., Inoue, M., Masatsugu, K., Korenaga, R., Ando, J., Nakao, K. Shear stress augments expression of C-type natriuretic peptide and adrenomedullin. Hypert., 1997, 29, 1296-1302.
53. Garayna, M., Martinez, A., Lee, S., Pio, R., An, W.G., Neckers, L., Trepel, J., Montuenga, L.M., Ryan, H., Johnson, R., Gassmann, M., Cuttitta, F. Hypoxia-inducible factor-1 (HIF-1) up-regulates adrenomedullin expression in human tumor cell lines during oxygen deprivation: a possible promotion mechanism of carcinogenesis. Mol. Endocrinol., 2000, 14, 848-862.
54. Champion, H.C., Akers, D.L., Santiago, J.A., Lambert. D.G., McNamara, D.B., Kadowitz PJ. Analysis of responses to human synthetic adrenomedullin and calcitonin gene-related peptides in the hindlimb vascular bed of the cat. Mol. Cell Biochem., 1997, 176, 5-11.
55. Shirai, M., Shimouchi, A., Ikeda, S., Ninomiya, I., Sunagawa, K., Kangawa, K., Matsuo, H. Vasodilator effects of adrenomedullin on small pulmonary arteries and veins in anaesthetized cats. Br. J. Pharmacol., 1997, 121, 679-686.
56. Eguchi, S., Hirata, Y., Kano, H., Sato, K., Watanabe, Y., Watanabe, T.X., Nakajima, K., Sakakibara, S., Marumo, F. Specific receptors for adrenomedullin in cultured rat vascular smooth muscle cells. FEBS Lett, 1994, 340, 226-230.
57. Ishizaka, Y., Ishizaka, Y., Tanaka, M., Kitamura, K., Kangawa, K., Minamino, N., Matsou, H., Eto, T. Adrenomedullin stimulates cyclic AMP formation in rat vascular smooth muscle cells. Biochem. Biophys. Res. Commun., 1994, 200, 642-646.
58. Feng, C.J., Kang, B., Kaye, A.D., Kadowitz, P.J., Nossaman, B.D. L-NAME modulates responses to adrenomedullin in the hindquarters vascular bed of the rat. Life. Sci., 1994, 55, L433-L438.
59. Venema, R.C., Sayegh, H.S., Kent, J.D., Harrison, D.G Identification, characterization, and comparison of the calmodulin-binding domains of the endothelial and inducible nitric oxide synthases. J. Biol. Chem., 1996, 271, 6435-6440.
60. Nishimatsu, H., Suzuki, E., Nagata, D., Moriyama, N., Satonaka, H., Walsh, K., Sata, M., Kangawa, K., Matsou, H., Goto, A., Kitamura, T., Hirata, Y. Adrenomedullin induces endothelium-dependent vasorelaxation via the phosphatidylinositol 3-kinase/Akt-dependent pathway in rat aorta. Circ. Res., 2001, 89, 63-70.
61. Owji, A.A., Smith, D.M., Coppock, H.A., Morgan, D.G., Bhogal, R., Ghatei, M.A., Bloom, S.R. An abundant and specific binding site for the novel vasodilator adrenomedullin in the rat. Endocrinology, 1995, 136, 2127-2134.
62. Lippton, H., Chang, J.K., Hao, Q., Summer, W., Hyman, A.L. Adrenomedullin dilates the pulmonary vascular bed in vivo. J. Appl. Physiol., 1994, 76, 2154-2156.
63. Christman, B.W., McPherson, C.D., Newman, J.H., King, G.A., Bernard, G.R., Groves, B.M., Loyd, J.E. An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N. Engl. J. Med., 1992, 327, 70-75.
64. Tuder, R.M., Cool, C.D., Geraci, M.W., Wang, J., Abman, S.H., Wright, L., Badesch, D., Voelkel, N.F. Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am. J. Respir. Crit. Care. Med., 1999, 159, 1925-1932.
65. Giaid, A., Saleh, D. Reduced expression of endothetial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N. Engl. J. Med., 1995, 333, 214-221.
66. Sata, M., Kakoki, M., Nagata, D., Nishimatsu, H., Suzuki, E., Aoyagi, T., Sugiura, S., Kojima, H., Nagano, T., Kangawa, K., Matsuo, H., Omata, M., Nagai, R., Hirata, Y. Adrenomedullin and nitric oxide inhibit human endothelial cell apoptosis via a cyclic GMP-independent mechanism. Hypertension, 2000, 36, 83-88.
67. Kim, W., Moon, S.O., Sung, M.J., Kim, S.H., Lee, S., So, J.N., Park, S.K. Angiogenic role of adrenomedullin through activation of Akt, mitogen-activated protein kinase, and focal adhesion kinase in endothetial cells. FASEB J, 2003, 17, 1937-1939.
68. Pietra, G.G., Edwards, W.D., Kay, J.M., Rich, S., Kernis, J., Schloo, B., Ayres, S.M., Bergofsky, E.H., Brundage, B.H., Detre, K.M. Histopathology of primary pulmonary hypertension. A qualitative and quantitative study of pulmonary blood vessels from 58 patients in the National Heart, Lung, and Blood Institute, Primary Pulmonary Hypertension Registry. Circulation, 1989, 80, 1198-1206.
69. Tuder, R.M., Groves, B., Badesch, D.B., Voelkel NF. Exuberant endothelial cell growth and elements of inflammation are present in plexiform lesions of pulmonary hypertension. Am.J. Pathol., 1994, 144, 275-285.
70. Kano, H., Kohno, M., Yasunari, K., Yokokawa, K., Horio, T., Ikeda, M., Minami, M., Hanehira, T., Takeda, T., Yoshikawa, J. Adrenomedullin as a novel antiproliferative factor of vascular smooth muscle cells. J. Hypertens., 1996, 14, 209-213.
71. Upton, P.D., Wharton, J., Coppock, H., Davie, N., Yang, X., Yacoub, M.H., Ghatei, M.A., Polak, J.M., Bloom, S.R., Smith, D.M., Morrell, N.W. Adrenomedullin expression and growth inhibitory effects in distinct pulmonary artery smooth muscle cell subpopulations. Am. J. Respir.Cell. Mol. Biol., 2001, 24, 170-178.
72. Horio, T., Kohno, M., Kano, H., Ikeda, M., Yasunari, K., Yokokawa, K., Minami, M., Takeda, T. Adrenomedullin as a novel antimigration factor of vascular smooth muscle cells. Circ. Res., 1995, 77, 660-664.
73. Yoshihara, F., Nishikimi, T., Horio, T., Yutani, C., Takishita, S., Matsuo, H., Ohe, T., Kangawa, K. Chronic infusion of adrenomedullin reduces pulmonary hypertension and lessens right ventricular hypertrophy in rats administered monocrotaline. Eur. J. Pharmacol., 1998, 355, 33-39.
74. Chini, E.N., Chini, C.C., Bolliger, C., Jougasaki, M., Grande, J.P., Burnett, J.C., Jr, Dousa J.P. Cytoprotective effects of adrenomedullin in glomerular cell injury: central role of cAMP signaling pathway. Kidney. Int., 1997, 52, 917-25.
75. Matsui, H., Shimosawa, T., Itakura, K., Guanqun, X., Ando, K., Fujita, T. Adrenomedullin can protect against pulmonary vascular remodeling induced by hypoxia. Circulation, 2004, 109, 2246-2251.
76. Heaton, J., Lin, B., Chang, J.K., Steinberg, S., Hyman, A., Lippton, H. Pulmonary vasodilation to adrenomedullin: a novel peptide in humans. Am. J. Physiol., 1995, 268, H2211-H2215.
77. Yang, B.C., Lippton, H., Gumusel, B., Hyman, A., Mehta, J.L. Adrenomedullin dilates rat pulmonary artery rings during hypoxia: role of nitric oxide and vasodilator prostaglandins. J. Cardiovasc. Pharmacol., 1996, 28, 458-462.
78. Rademaker, M.T., Charles, C.J., Lewis, L.K., Yandle, T.G., Cooper, G.J., Coy, D.H., Richards, A.M., Nicholls, M.G. Beneficial hemodynamic and renal effects of adrenomedullin in an ovine model of heart failure. Circulation, 1997, 96, 1983-1990.
79. Nagaya, N., Satoh, T., Nishikimi, T., Uematsu, M., Furuichi, S., Sakamaki, F., Oya, H., Kyotani, S., Nakanishi, N., Goto, Y., Masuda, Y., Miyatake, K., Kangawa, K. Hemodynamic, renal, and hormonal effects of adrenomedullin infusion in patients with congestive heart failure. Circulation, 2000, 101, 498-503.
80. Nagaya, N., Nishikimi, T., Uematsu, M., Satoh, T., Oya, H., Kyotani, S., Sakamaki, F., Ueno, K., Nakanishi, N., Miyatake, K., Kangawa, K. Haemodynamic and hormonal effects of adrenomedullin in patients with pulmonary hypertension. Heart, 2000, 84, 653-658.
81. Nishikimi, T., Horio, T., Yoshihara, F., Nagaya, N., Matsuo, H., Kangawa, K. Effect of adrenomedullin on dAMP and cGMP levels in rat cardiac myocytes and nonmyocytes. Eur. J. Pharmacol., 1998, 353, 337-344.
82. Ihara, T., Ikeda, U., Tate, Y., Ishibashi, S., Shimada, K. Positive inotropic effects of adrenomedullin on rat papillary muscle. Eur. J. Pharmacol., 2000, 390, 167-172.
83. Szokodi, I., Kinnunen, P., Tavi, P., Weckstrom, M., Toth, M., Ruskoaho, H. Evidence for cAMP-independent mechanisms mediating the effects of adrenomedullin, a new inotropic peptide. Circuiation, 1998, 97, 1062-1070.
84. Hoeper, M.M., Schwarze, M., Ehlerding, S., Adler-Schuermeyer, A., Spiekerkoetter, E., Niedermeyer, J., Hamm, M., Fabel, H. Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. N. Engl. J. Med., 2000, 342, 1866-1870.
85. Walmrath, D., Schneider, T., Pitch, J., Grimminger, F., Seeger, W. Aerosolised prostacyclin in adult respiratory distress syndrome. Lancet, 1993, 342, 961-962.
86. Nagaya, N., Okumura, H., Uematsu, M., Shimizu, W., Ono, F., Shirai, M., Mori, H., Miyatake, K., Kangawa, K. Repeated inhalation of adrenomedullin ameliorates pulmonary hypertension and survival in monocrotaline rats. Am. J. Physiol. Heart. Circ. Physiol., 2003, 285, 112125-112131.
87. von der Hardt, K., Kandler, M.A., Chada, M., Cobra, A., Schoof, E., Amann, K., Rascher, W., Dotsch J. Brief adrenomedullin inhalation leads to sustained reduction of pulmonary artery pressure. Eur. Respir. J., 2004, 24, 615-623.
88. Yanagisawa, M., Kurihara, H., Kimura, S., Tomobe, Y., Kobayashi, M., Mitsui, Y., Yazaki, Y., Goto, K., Masaki, T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature, 1988, 332, 411-415.
89. Stewart, D.J., Levy, R.D., Cernacek, P., Langleben D. Increased plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease? Ann. Intern. Med., 1991, 114, 464-469.
90. Nootens, M., Kaufmann, E., Rector, T., Toher, C., Judd, D., Francis, G.S., Rich, S. Neurohormonal activation in patients with right ventricular failure from pulmonary hypertension: relation to hemodynamic variables and endothelin levels. J. Am. Coll. Cardiol., 1995, 26, 1581-1585.
91. Rubens, C., Ewert, R., Halank, M., Wensel, R., Orzechowski, H.D., Schultheiss, H.P., Hoeffken G. Big endothelin-1 and endothelin-1 plasma levels are correlated with the severity of primary pulmonary hypertension, Chest, 2001, 120, 1562-1569.
92. Collados, M.T., Velazquez, B., Borbolla, J.R., Sandoval, J., Masso, F., Montano, L.F., Guarner V. Endothelin-1 and functional tissue factor: a possible relationship with severity in primary pulmonary hypertension. Heart Vessels, 2003, 18, 12-17.
93. Giaid, A., Yanagisawa, M., Langleben, D., Michel, R.P., Levy, R., Shennib, H., Kimura, S., Masaki, T., Duguid, W.P., Stewart, D.J. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N. Engl. J. Med., 1993, 328, 1732-1739.
94. Nagaya, N., Kyotani, S., Uematsu, M., Ueno, K. Oya, H., Nakanishi, N., Shirai, M., Mori, H., Miyatake, K., Kangawa, K. Effects of adrenomedullin inhalation on hemodynamics and exercise capacity in patients with idiopathic pulmonary arterial hypertension. Circulation, 2004, 109, 351-356.
95. Asahara, T., Murohara, T., Sullivan, A., Silver, M., van der Zee, R., Li, T., Witzenbichler, B., Schatteman, G., Isner JM. Isolation of putative progenitor endothelial cells for angiogenesis. Science, 1997, 275, 964-967.
96. Takahashi, T., Kalka, C., Masuda, H., Chen, D., Silver, M., Kearney, M., Magner, M., Isner, J.M., Asahara, T. Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat. Med., 1999, 5, 434-438.
97. Gill, M., Dias, S., Hattori, K., Rivera, M.L., Hicklin, D., Witte, L., Girardi, L., Yurt, R., Himel, H., Rafii, S. Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells. Circ. Res., 2001, 88, 167-174.
98. Kawamoto, A., Gwon, H.C., Iwaguro, H., Yamaguchi, J.L, Uchida, S., Masuda, H., Silver, M., Ma, H., Kearney, M., Isner, J.M., Asahara, T. Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia. Circulation, 2001, 103, 634-637.
99. Murohara, T., Ikeda, H., Duan, J., Shintani, S., Sasaki, K., Eguchi, H., Onitsuka, I., Matsui, K., Imaizumi, T. Transplanted cord blood-derived endothelial precursor cells augment postnatal neovascularization. J. Clin. Invest., 2000, 105, 1527-1536.
100. Shintani, S., Murohara, T., Ikeda, H., Ueno, T., Sasaki, K., Duan, J., Imaizumi, T. Augmentation of postnatal neovascularization with autologous bone marrow transplantation. Circulation, 2001, 103, 897-903.
101. Tateishi-Yuyama. E., Matsubara, H., Murohara. T., Ikeda, U., Shintani, S., Masaki, H., Amano, K., Kishimoto, Y., Yoshimoto, K., Akashi, H., Shimada, K., Iwasaka, T., Imaizumi, T. Therapeutic Angiogenesis using Cell Transplantation (TACT) Study Investigators. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet, 2002, 360, 427-435.
102. Nagaya, N., Kangawa, K., Kanda, M., Uematsu, M., Horio, T., Fukuyama, N., Hino. J., Harada-Shiba, M., Okumura, H., Tabata, Y., Mochizuki, N., Chiba, Y., Nishioka, K., Miyatake., K., Asahara, T., Hara, H., Mori, H. Hybrid cell-gene therapy for pulmonary hypertension based on phagocytosing action of endothelial progenitor cells. Circulation, 2003, 108, 889-895.
103. Murasawa, S., Llevadot, J., Silver, M., Isner, J.M., Losordo, D.W., Asahara, T. Constitutive human telomerase reverse transcriptase expression enhances regenerative properties of endothelial progenitor cells. Circulation, 2002, 106, 1133-1139.
104. Fukunaka, Y., Iwanaga, K., Morimoto, K., Kakemi, M., Tabata, Y. Controlled release of plasmid DNA from cationized gelatin hydrogels based on hydrogel degradation. J. Control. Release, 2002, 80, 333-343.
105. Kushibiki, T., Tomoshige, R., Fukunaka, Y., Kakemi, M., Tabata, Y. In vivo release and gene expression of plasmid DNA by hydrogels of gelatin with different cationization extents. J. Cont. Release, 2003, 90, 207-216.
106. Kasahara, H., Tanaka, E., Fukuyama, N., Sato, E., Sakamoto, H., Tabata, Y., Ando, K., Iseki, H., Shinozaki, Y., Kimura, K., Kuwabara, E., Koide, S., Nakazawa, H., Mori, H. Biodegradable gelatin hydrogel potentiates the angiogenic effect of fibroblast growth factor 4 plasmid in rabbit hindlimb ischemia. J. Am. Coll. Cardiol., 2003, 41, 1056-1062.
107. Tokunaga, N., Nagaya, N., Shirai, M., Tanaka, E., Ishibashi-Ueda, H., Harada-Shiba, M., Kanda, M., Ito, T., Shimizu, W., Tabata, Y., Uematsu, M., Nishigami, K., Sano, S., Kangawa, K., Mori H. Adrenomedullin gene transfer induces therapeutic angiogenesis in a rabbit model of chronic hind limb ischemia: benefits of a novel nonviral vector, gelatin. Circulation, 2004, 109, 526-531.