Circulation Research, Vol 66, 891-899, Copyright © 1990 by American Heart Association

ARTICLES

Angiotensins and the failing heart. Enhanced positive inotropic response to angiotensin I in cardiomyopathic hamster heart in the presence of captopril

H Hirakata, FM Fouad-Tarazi, FM Bumpus, M Khosla, B Healy, A Husain, H Urata and H Kumagai
Department of Heart and Hypertension Research, Cleveland Clinic Foundation, OH 44195-5069.

We examined the hypothesis that the positive inotropic effect of angiotensin I (Ang I) may be retained in the presence of angiotensin converting enzyme inhibitors so that it may have a direct beneficial effect on the heart. Accordingly, isolated perfused hearts (Langendorff preparation) of 300-day-old cardiomyopathic hamsters (a model of spontaneous cardiomyopathy) and age-matched normal hamsters (controls) were infused with Ang I in the presence of captopril; propranolol was added to the perfusing medium to block catecholamine-mediated effects of angiotensins on the heart. Left ventricular developed pressure and the rate of increase in left ventricular developed pressure increased significantly (p less than 0.001) in both the cardiomyopathic and the normal hamster heart despite concomitant reduction in myocardial flow rate favoring a direct inotropic effect of Ang I in both normal and myopathic hearts; these changes were significantly higher by almost threefold in the cardiomyopathic than in the normal hamsters (p less than 0.01) and were blocked by the angiotensin II (Ang II) antagonist [Sar1,Thr8]Ang II. Comparing dose-left ventricular contractility response curves for Ang I and Ang II, ED50 for responses was identical in both normal and myopathic hearts, whereas peak responses to Ang II were double those to Ang I in normal hearts but were almost identical in the myopathic hearts. Binding of [125I]Ang II in six cardiomyopathic and four normal hamster hearts was of high affinity, but there was no evidence for Ang I-saturable high-affinity binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				S. Wiese, T. Breyer, A. Dragu, R. Wakili, T. Burkard, S. Schmidt-Schweda, E.-M. Fuchtbauer, U. Dohrmann, F. Beyersdorf, D. Radicke, et al. Gene Expression of Brain Natriuretic Peptide in Isolated Atrial and Ventricular Human Myocardium : Influence of Angiotensin II and Diastolic Fiber Length Circulation, December 19, 2000; 102(25): 3074 - 3079. [Abstract] [Full Text] [PDF]

				H. Urata Pathological involvement of chymase-dependent angiotensin II formation in the development of cardiovascular disease Journal of Renin-Angiotensin-Aldosterone System, June 1, 2000; 1(2_suppl): S35 - S37. [Abstract] [PDF]

				N. R. Bastien, A.-V. Juneau, J. Ouellette, and C. Lambert Chronic AT1 receptor blockade and angiotensin-converting enzyme (ACE) inhibition in (CHF 146) cardiomyopathic hamsters: effects on cardiac hypertrophy and survival Cardiovasc Res, July 1, 1999; 43(1): 77 - 85. [Abstract] [Full Text] [PDF]

				B. K. Slinker, Y. Wu, A. J. Brennan, K. B. Campbell, and J. W. Harding Angiotensin IV has mixed effects on left ventricle systolic function and speeds relaxation Cardiovasc Res, June 1, 1999; 42(3): 660 - 669. [Abstract] [Full Text] [PDF]

				H. Nishimura, H. Buikema, O. Baltatu, D. Ganten, and H. Urata Functional evidence for alternative ANG II-forming pathways in hamster cardiovascular system Am J Physiol Heart Circ Physiol, October 1, 1998; 275(4): H1307 - H1312. [Abstract] [Full Text] [PDF]

				M. Akasu, H. Urata, A. Kinoshita, M. Sasaguri, M. Ideishi, and K. Arakawa Differences in Tissue Angiotensin II–Forming Pathways by Species and Organs In Vitro Hypertension, September 1, 1998; 32(3): 514 - 520. [Abstract] [Full Text] [PDF]

				E. A. Garrison, H. C. Champion, and P. J. Kadowitz [Pro11,D-Ala12]angiotensin I has rapid onset vasoconstrictor activity in the cat Am J Physiol Endocrinol Metab, December 1, 1997; 273(6): E1059 - E1064. [Abstract] [Full Text] [PDF]

				K. Tsuchiya, M. Horie, M. Watanuki, C. A. Albrecht, K. Obayashi, H. Fujiwara, and S. Sasayama Functional Compartmentalization of ATP Is Involved in Angiotensin II–Mediated Closure of Cardiac ATP-Sensitive K+ Channels Circulation, November 4, 1997; 96(9): 3129 - 3135. [Abstract] [Full Text]

				P. Sil Subha Sen Angiotensin II and Myocyte Growth : Role of Fibroblasts Hypertension, August 1, 1997; 30(2): 209 - 216. [Abstract] [Full Text]

				C. Lambert, Y. Massillon, and S. Meloche Upregulation of Cardiac Angiotensin II AT1 Receptors in Congenital Cardiomyopathic Hamsters Circ. Res., November 1, 1995; 77(5): 1001 - 1007. [Abstract] [Full Text]