Comparison of the effects of angiotensin II receptor antagonist monotherapy and combination therapy with a diuretic on cardiac function in spontaneously hypertensive rats.

Abstract

Losartan, an angiotensin II receptor blocker (ARB), has been reported to promote sodium excretion and show an enhanced antihypertensive effect when used in combination with hydrochlorothiazide (HCTZ). We investigated the effects of losartan monotherapy and combination therapy together with HCTZ on cardiac function in hypertensive rats using echocardiography. Spontaneously hypertensive rats (n=21) fed on high-salt diet (8% NaCl) for 13weeks were randomly assigned to rats without medication (HS, n=7), those medicated with ARB (ARB, losartan 30mg/kg/day, n=8), and those with ARB and HCTZ (ARB+HCTZ, losartan 30mg/kg/day+HCTZ 10mg/kg/day, n=6). Blood pressure measurements and echocardiography were performed at 13, 17, and 29weeks of age. After the end of the protocol, the proportion of cardiac muscle fibrosis was measured histologically. In the HS group, blood pressure and left ventricular mass/body weight (LV mass/BW) increased, and % fractional shortening (%FS) and early diastolic mitral annular velocity (e') decreased significantly with age. In the ARB group, although blood pressure and %FS were maintained, LV mass/BW increased with age as in the HS group, and e' decreased. In the ARB+HCTZ group, blood pressure decreased and LV mass/BW, %FS, and e' were maintained. The progression of myocardial fibrosis was clearly prevented in rats treated with ARB. ARB was shown to inhibit systolic disorder and myocardial fibrosis in hypertensive rats. Combination therapy proved to be more effective than monotherapy and is also effective in inhibiting diastolic disorders.