Cardiac renin-angiotensin system: role in development of pressure-overload hypertrophy.
Recent studies are reviewed dealing with the putative roles of the cardiac renin-angiotensin system in the development of pressure-overload hypertrophy and the subsequent transition from adaptive hypertrophy to diastolic dysfunction, impaired systolic function and cardiac failure. The results of these studies, which employed the aortic banded rat model of cardiac hypertrophy, indicate that the intracardiac conversion of angiotensin I (Ang I) to angiotensin II (Ang II) is significantly increase in hypertrophied hearts compared with hearts from age-matched, sham-operated controls, and that Ang II may have a direct effect of slowing relaxation and altering diastolic tone in the hypertrophied heart. Furthermore, in patients with aortic stenosis and severe baseline abnormalities of diastolic relaxation and filling, acute intracardiac angiotensin-converting enzyme (ACE) inhibition, totally in the absence of any systemic effect on neurohormones, improved diastolic function. ACE inhibition was found to reduce net ACE activity and to increase plasma renin activity in aortic banded animals compared with untreated banded controls. There was also a trend for circulating noradrenaline levels to be increased at this stage of transition to failure in the untreated banded animals but ACE inhibition tended to restore the levels back to normal. In ACE inhibitor-treated animals, left ventricular (LV) diastolic pressure was significantly reduced, despite the persistent elevation of systolic pressure, but not yet restored completely to normal. In untreated, banded animals the transition to cardiac failure was evidenced as an increase in both systolic and diastolic dimensions with a reduction in fractional shortening.(ABSTRACT TRUNCATED AT 250 WORDS)
Lorell
B H
BH
Charles A Dana Research Institute, Boston, Massachusetts, USA.
D000803:Angiotensin I / Q000502:physiology; D000804:Angiotensin II / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001024:Aortic Valve Stenosis / Q000503:physiopathology; D001794:Blood Pressure; D006332:Cardiomegaly / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D006333:Heart Failure / Q000503:physiopathology; D006801:Humans; D009200:Myocardial Contraction / Q000502:physiology; D051381:Rats; D012084:Renin-Angiotensin System / Q000502:physiology*; D016277:Ventricular Function, Left / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D000803:Angiotensin I