Renin-angiotensin system and minoxidil-induced cardiac hypertrophy in rats.
Besides cardiac volume overload, cardiac sympathetic activity and the renin-angiotensin system (RAS) are activated by arterial vasodilators such as minoxidil. To evaluate the possible involvement of the RAS in the development of minoxidil-induced cardiac hypertrophy, we assessed in normotensive rats minoxidil-induced changes in cardiac and plasma renin activity (PRA) and the potential of chronic treatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril and the nonpeptide angiotensin II receptor blocker losartan to prevent minoxidil-induced cardiac hypertrophy. PRA increased in parallel with the increase in cardiac filling pressures and development of cardiac hypertrophy, whereas the increase in cardiac renin activity was delayed as compared with these changes. Losartan did not decrease left ventricular end-diastolic pressure (LVEDP) but prevented the remodeling of the heart by minoxidil. In contrast, enalapril nearly normalized LVEDP but did not affect the hypertrophic response of the heart. The losartan data indicate that the RAS is involved in the minoxidil-induced cardiac hypertrophy either directly (e.g., by mediating the hypertrophic response of the heart to cardiac volume overload) or indirectly (e.g., by potentiating cardiac sympathetic activity). The ineffectiveness of enalapril has no obvious explanation but may possibly indicate ineffective blockade of angiotensin II formation in the heart in this model.
Ruzicka
M
M
Hypertension Unit, University of Ottawa Heart Institute, Ontario, Canada.
Leenen
F H
FH
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000139:chemically induced / Q000503:physiopathology*; D004656:Enalapril / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan; D008297:Male; D008914:Minoxidil / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects
D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D008914:Minoxidil; D004656:Enalapril; D012083:Renin; D019808:Losartan