Effects of the angiotensin II receptor antagonist losartan on 24-hour blood pressure profiles of primary and secondary hypertensive rats.

Abstract

Primary and secondary hypertension differ with regard to circadian blood pressure (BP) profiles. To evaluate the contribution of the renin-angiotensin system (RAS) to circadian BP regulation, we studied cardiovascular effects of the angiotensin II (AII) receptor antagonist losartan and the angiotensin-converting enzyme (ACE) inhibitor enalapril in animal models of primary and secondary hypertension after morning and evening dosing. Systolic/diastolic BP (SBP/DBP) and heart rate (HR) were measured telemetrically in spontaneously hypertensive rats (SHR) and transgenic hypertensive rats (TGR[mRen-2]27). Losartan (0.3 to 30 mg/kg) or enalapril maleate (10 mg/kg) were injected intraperitoneally (i.p.) either at 0700 or 1900 h. Baseline SBP/DBP and HR showed significant circadian rhythmicity in both strains. The 24-h means in SBP/DBP were 190/127 mm Hg in SHR and 200/139 mm Hg in TGR. TGR showed a reversed circadian profile in BP, with peaks occurring during the daily resting period, whereas HR peaked at night. Losartan reduced BP dose dependently; reductions in TGR were significantly greater and obtained at 30-fold lower doses than in SHR. Maximum decreases induced by losartan were similar to those induced with enalapril 10 mg/kg. Both drugs reduced BP in TGR more effectively when applied at 0700 than at 1900 h, resulting in a normalized circadian BP profile. Our results demonstrate that the RAS is involved in both the pathomechanism of hypertension and in the inverse circadian BP pressure pattern in TGR.