Isoproterenol-induced cardiac hypertrophy: role of circulatory versus cardiac renin-angiotensin system

To assess the possible contribution of the circulatory and cardiac renin-an giotensin system (RAS) to the cardiac hypertrophy induced by a beta -agonis t, the present study evaluated the effects of isoproterenol, alone or combi ned with an angiotensin I-converting enzyme inhibitor or AT(1) receptor blo cker, on plasma and LV renin activity, ANG I, and ANG II, as well as left v entricular (LV) and right ventricular (RV) weight. Male Wistar rats receive d isoproterenol by osmotic minipump subcutaneously and quinapril or losarta n once daily by gavage. Plasma and LV ANGs were measured by radioimmunoassa y after separation by HPLC. Isoproterenol alone decreased blood pressure, m ore markedly when combined with losartan or quinapril. Isoproterenol signif icantly increased LV and RV weight and total collagen. Neither losartan nor quinapril inhibited the increases in LV or RV weight. Losartan prevented t he increase in RV collagen but enhanced the increase in LV collagen. Isopro terenol increased plasma renin, ANG I, and ANG II three- to fourfold. Isopr oterenol combined with losartan or quinapril, caused marked further increas es except for a significant decrease in plasma ANG II with quinapril. Isopr oterenol alone did not increase LV ANG II and, combined with losartan or qu inapril, actually decreased LV ANG II. These results indicate that isoprote renol-induced cardiac hypertrophy is associated with clear increases in pla sma 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 cardi ac hypertrophy. These findings do not support a role for the circulatory or cardiac RAS in the cardiac trophic responses to beta -receptor stimulation .