Circulation Research, Vol 67, 1355-1364, Copyright © 1990 by American Heart Association

ARTICLES

Remodeling of the rat right and left ventricles in experimental hypertension

CG Brilla, R Pick, LB Tan, JS Janicki and KT Weber
Cardiovascular Institute, Michael Reese Hospital, University of Chicago Pritzker School of Medicine, Ill.

Pathological left ventricular hypertrophy in renovascular hypertension is associated with the accumulation of fibrillar collagen within the extracellular space and around intramyocardial coronary arteries. Even though the angiotensin converting enzyme inhibitor captopril was previously found to attenuate this interstitial and perivascular fibrosis, the relative importance of arterial and ventricular systolic pressures versus circulating angiotensin II (AII) and aldosterone (AL) in promoting hypertrophy and collagen accumulation in renovascular hypertension is uncertain. By drawing on the in-parallel arrangement of the right and left ventricles, with respect to their coronary circulation, and the in-series mechanical alignment of the ventricles, with a pressure-overloaded left and a normotensive right ventricle, this study sought to address this uncertainty. Three models of experimental hypertension, each having a different circulating AII and AL profile, were examined and compared with their controls: renovascular hypertension, where both AII and AL are increased; infrarenal aorta banding, where AII and AL are normal; and a chronic infusion of AL, where AII is suppressed or normal and AL is increased. In renovascular hypertension, as well as with AL, we found a significant rise in the interstitial collagen volume fraction and perivascular collagen area of the pressure-overloaded, hypertrophied left ventricle as well as the normotensive, nonhypertrophied right ventricle. This remodeling was not seen in either ventricle with infrarenal aorta banding despite comparable systemic hypertension and left ventricular hypertrophy. Thus, in experimental arterial hypertension in the rat, myocyte and nonmyocyte compartments of the myocardium are under separate controls: myocyte hypertrophy is most closely related to ventricular loading while circulating AII and AL, acting alone or in concert with other humoral factors, regulate the accumulation of collagen within the right and left ventricles.

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				C. G Brilla Renin-angiotensin-aldosterone system and myocardial fibrosis Cardiovasc Res, July 1, 2000; 47(1): 1 - 3. [Full Text] [PDF]

				J. E. Bishop, L. A. Kiernan, H. E. Montgomery, P. Gohlke, and J. R. McEwan Raised blood pressure, not renin-angiotensin systems, causes cardiac fibrosis in TGR m(Ren2)27 rats Cardiovasc Res, July 1, 2000; 47(1): 57 - 67. [Abstract] [Full Text] [PDF]

				C. G Brilla Regression of myocardial fibrosis in hypertensive heart disease: diverse effects of various antihypertensive drugs Cardiovasc Res, May 1, 2000; 46(2): 324 - 331. [Abstract] [Full Text] [PDF]

				M. Brink, J. Chrast, S. R. Price, W. E. Mitch, and P. Delafontaine Angiotensin II Stimulates Gene Expression of Cardiac Insulin-Like Growth Factor I and Its Receptor Through Effects on Blood Pressure and Food Intake Hypertension, November 1, 1999; 34(5): 1053 - 1059. [Abstract] [Full Text] [PDF]

				H. Karam, J.-P. Clozel, P. Bruneval, M.-F. Gonzalez, and J. Menard Contrasting Effects of Selective T- and L-Type Calcium Channel Blockade on Glomerular Damage in DOCA Hypertensive Rats Hypertension, October 1, 1999; 34(4): 673 - 678. [Abstract] [Full Text] [PDF]

				B. Pitt, F. Zannad, W. J. Remme, R. Cody, A. Castaigne, A. Perez, J. Palensky, J. Wittes, and The Randomized Aldactone Evaluation Study Investig The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure N. Engl. J. Med., September 2, 1999; 341(10): 709 - 717. [Abstract] [Full Text] [PDF]

				C. Delcayre and J.-S. Silvestre Aldosterone and the heart: towards a physiological function? Cardiovasc Res, July 1, 1999; 43(1): 7 - 12. [Full Text] [PDF]

				S. Lamparter, Y. Sun, and K. T Weber Angiotensin II receptor blockade during gestation attenuates collagen formation in the developing rat heart Cardiovasc Res, July 1, 1999; 43(1): 165 - 172. [Abstract] [Full Text] [PDF]

				J.-S. Silvestre, C. Heymes, A. Oubenaissa, V. Robert, B. Aupetit-Faisant, A. Carayon, B. Swynghedauw, and C. Delcayre Activation of Cardiac Aldosterone Production in Rat Myocardial Infarction : Effect of Angiotensin II Receptor Blockade and Role in Cardiac Fibrosis Circulation, May 25, 1999; 99(20): 2694 - 2701. [Abstract] [Full Text] [PDF]

				A. Morimoto, T. Nishikimi, F. Yoshihara, T. Horio, N. Nagaya, H. Matsuo, K. Dohi, and K. Kangawa Ventricular Adrenomedullin Levels Correlate With the Extent of Cardiac Hypertrophy in Rats Hypertension, May 1, 1999; 33(5): 1146 - 1152. [Abstract] [Full Text] [PDF]

				H. M. Thai, H. T. Van, M. A. Gaballa, S. Goldman, and T. E. Raya Effects of AT1 receptor blockade after myocardial infarct on myocardial fibrosis, stiffness, and contractility Am J Physiol Heart Circ Physiol, March 1, 1999; 276(3): H873 - H880. [Abstract] [Full Text] [PDF]

				P. E. McEwan, G. A. Gray, L. Sherry, D. J. Webb, and C. J. Kenyon Differential Effects of Angiotensin II on Cardiac Cell Proliferation and Intramyocardial Perivascular Fibrosis In Vivo Circulation, December 15, 1998; 98(24): 2765 - 2773. [Abstract] [Full Text] [PDF]

				H. C. M. Yu, L. M. Burrell, M. J. Black, L. L. Wu, R. J. Dilley, M. E. Cooper, and C. I. Johnston Salt Induces Myocardial and Renal Fibrosis in Normotensive and Hypertensive Rats Circulation, December 8, 1998; 98(23): 2621 - 2628. [Abstract] [Full Text] [PDF]

				M. F. M. van Oosterhout, F. W. Prinzen, T. Arts, J. J. Schreuder, W. Y. R. Vanagt, J. P. M. Cleutjens, and R. S. Reneman Asynchronous Electrical Activation Induces Asymmetrical Hypertrophy of the Left Ventricular Wall Circulation, August 11, 1998; 98(6): 588 - 595. [Abstract] [Full Text] [PDF]

				S. Sandmann, H. Spitznagel, O. Chung, Qin-Gui Xia, S. Illner, G. Janichen, B. Rossius, M. J.A.P Daemen, and T. Unger Effects of the calcium channel antagonist mibefradil on haemodynamic and morphological parameters in myocardial infarction-induced cardiac failure in rats Cardiovasc Res, August 1, 1998; 39(2): 339 - 350. [Abstract] [Full Text] [PDF]

				J. F. Ramnrez-Gil, P. Trouve, N. Mougenot, A. Carayon, P. Lechat, and D. Charlemagne Modifications of myocardial Na+,K+-ATPase isoforms and Na+/Ca2+ exchanger in aldosterone/salt-induced hypertension in guinea pigs Cardiovasc Res, May 1, 1998; 38(2): 451 - 462. [Abstract] [Full Text] [PDF]