The cardiac renin-angiotensin system in heart failure.
The success of angiotensin-converting enzyme (ACE) inhibitors in reducing cardiovascular morbidity and mortality rates has led to a reexamination of the role of the renin-angiotensin system in pathophysiology. Ventricular dysfunction leading to congestive cardiac failure is associated with sequential activation of the sympathetic system and increases in plasma atrial natriuretic peptide; however, increases in plasma renin and aldosterone do not occur until very late. The renin-angiotensin system is now regarded as both a circulating and tissue hormonal system. All components of the renin-angiotensin system have been detected in the heart. ACE is localized in discrete areas of the heart, including the cardiac valves, coronary vessels, atria, and myocardium. After experimental myocardial infarction in the rat, although plasma renin and aldosterone levels are not increased, ACE in the myocardium is markedly increased. Treatment with ACE inhibitors suppresses cardiac ACE and is associated with hemodynamic improvement, reversal of the neurohumoral activation, prevention of ventricular dilatation, and remodeling and reduction in mortality rates. These results suggest that the beneficial effects of ACE inhibitors in treating congestive cardiac failure, preventing ventricular remodeling, and regressing left ventricular hypertrophy may involve not only reducing preload and afterload but also suppressing the local cardiac renin-angiotensin system.
Johnston
C I
CI
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
Fabris
B
B
Yoshida
K
K
D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D009206:Myocardium / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II