EFFECTS OF VALSARTAN AND HYDROCHLOROTHIAZIDE ALONE AND IN COMBINATIONON BLOOD-PRESSURE AND HEART-RATE IN CONSCIOUS-TELEMETERED SPONTANEOUSLY HYPERTENSIVE RATS (SHR)

The purpose of this study was to examine the effectiveness of combined administration of the angiotensin AT, receptor antagonist valsartan, with the diuretic hydrochlorothiazide (HCTZ), on blood pressure in con scious spontaneously hypertensive rats (SHR), Both drugs were administ ered continuously via subcutaneously implanted osmotic minipumps alone or in combination for a period of 2 weeks. Mean arterial pressure and heart rate were monitored throughout the infusion interval by means o f chronically-implanted radiotransmitters. Coadministration of a diure tic with valsartan potentiated the blood pressure lowering effect in c onscious SHR. Responses varied in magnitude from additive (valsartan a t 1 mg/kg/day + hydrochlorothiazide at 3 and 10 mg/kg/day) to synergis tic (valsartan at 3 mg/kg/day + hydrochlorothiazide at 10 mg/kg/day). The greater blood pressure lowering seen in SHR receiving combination therapy was associated with only a transient increase in heart rate. A similar potentiation of the antihypertensive effect was seen during c oadministration of hydrochlorothiazide (HCTZ) with the angiotensin con verting enzyme inhibitor benazeprilat. Additivity was noted with benaz eprilat at 1 mg/kg/day + hydrochlorothiazide at 3 mg/kg/day, whereas a higher dose of HCTZ resulted in a synergistic response. These finding s suggest that the similar results obtained with angiotensin convertin g enzyme inhibitors and AT, receptor antagonists are due to the capaci ty to which diuretic-induced activation of the renin angiotensin syste m occurs. (C) 1998 American Journal of Hypertension, Ltd.