Isoproterenol-induced cardiac hypertrophy: role of circulatory versus cardiac renin-angiotensin system.
To assess the possible contribution of the circulatory and cardiac renin-angiotensin system (RAS) to the cardiac hypertrophy induced by a beta-agonist, the present study evaluated the effects of isoproterenol, alone or combined with an angiotensin I-converting enzyme inhibitor or AT(1) receptor blocker, on plasma and LV renin activity, ANG I, and ANG II, as well as left ventricular (LV) and right ventricular (RV) weight. Male Wistar rats received isoproterenol by osmotic minipump subcutaneously and quinapril or losartan once daily by gavage. Plasma and LV ANGs were measured by radioimmunoassay after separation by HPLC. Isoproterenol alone decreased blood pressure, more markedly when combined with losartan or quinapril. Isoproterenol significantly increased LV and RV weight and total collagen. Neither losartan nor quinapril inhibited the increases in LV or RV weight. Losartan prevented the increase in RV collagen but enhanced the increase in LV collagen. Isoproterenol increased plasma renin, ANG I, and ANG II three- to fourfold. Isoproterenol combined with losartan or quinapril, caused marked further increases except for a significant decrease in plasma ANG II with quinapril. Isoproterenol alone did not increase LV ANG II and, combined with losartan or quinapril, actually decreased LV ANG II. These results indicate that isoproterenol-induced cardiac hypertrophy is associated with clear increases in plasma ANG II, but not in LV ANG II. Both losartan and quinapril lower LV ANG II below control levels, but do not prevent the isoproterenol-induced cardiac hypertrophy. These findings do not support a role for the circulatory or cardiac RAS in the cardiac trophic responses to beta-receptor stimulation.
Leenen
F H
FH
Hypertension Unit, University of Ottawa Heart Institute, Ontario, Canada. fleenen@ottawaheart.ca
White
R
R
Yuan
B
B
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D003094:Collagen / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D000077583:Quinapril; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000378:metabolism; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D044005:Tetrahydroisoquinolines
D000318:Adrenergic beta-Agonists; D000959:Antihypertensive Agents; D007546:Isoquinolines; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D044005:Tetrahydroisoquinolines; D000804:Angiotensin II; D003094:Collagen; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D019808:Losartan; D007545:Isoproterenol; D000077583:Quinapril