EFFECTS OF THE ANGIOTENSIN-II RECEPTOR ANTAGONIST LOSARTAN ON 24-HOURBLOOD-PRESSURE PROFILES OF PRIMARY AND SECONDARY HYPERTENSIVE RATS

Primary and secondary hypertension differ with regard to circadian blo od pressure (BP) profiles. To evaluate the contribution of the renin-a ngiotensin system (RAS) to circadian BP regulation, we studied cardiov ascular effects of the angiotensin II (AII) receptor antagonist losart an 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) we re measured telemetrically in spontaneously hypertensive rats (SHR) an d 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 signifi cant 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 rever sed circadian profile in BP, with peaks occurring during the daily res ting period, whereas HR peaked at night. Losartan reduced BP dose depe ndently; 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 red uced BP in TGR more effectively when applied at 0700 than at 1900 h, r esulting in a normalized circadian BP profile. Our results demonstrate that the RAS is involved in both the pathomechanism of hypertension a nd in the inverse circadian BP pressure pattern in TGR.