COMPARISON OF THE EFFECTS OF ANGIOTENSIN-II, LOSARTAN, AND ENALAPRIL ON BAROREFLEX CONTROL OF HEART-RATE IN CONSCIOUS RABBITS

We compared the effects of angiotensin II (AII), enalapril, and losart an given by acute intravenous (i.v.) injection, on cardiac baroreflex sensitivity in two groups of conscious normotensive rabbits bred for h igh gain [>5 beats/min/mm Hg] (group I) and low gain [<4 beats/min/mm Hg] (group II) of the mean arterial blood pressure-heart rate (MAP/HR) relationship, respectively. Full sigmoid barocurves were produced in 62 rabbits by i.v. injection of phenylephrine (PE 1-15 mu g/kg) and ni troglycerin (NTG 1-20 mu g/kg) after pretreatment with saline or with AII, enalapril, or losartan. In group II, AII had a biphasic effect on baroreflex sensitivity; at 10 and 50 ng/ kg/min, it increased the gai n from 3.47 +/- 0.21 to 4.75 +/- 0.44 and 5.13 +/- 0.28 beats/min/mm H g (p < 0.05 and p < 0.025, respectively), but had no effect at 100 ng/ kg/min. BP increased in these rabbits by 11.5, 10, and 23 mm Hg after these three doses. In group I, AII 50 ng/kg/min increased BP by 8 mm H g, (p < 0.05) and decreased gain from 6.13 +/- 0.32 to 4.75 +/- 0.44 b eats/min/mm Hg (p < 0.01). Therefore, AII 50 ng/kg/min equalized baror eflex sensitivity in the two groups. In group II, both losartan (2.5 m g/kg) and enalapril (1 mg/kg) decreased BP by 8.6 +/- 1.0 and 10.2 +/- 2.1 mm Hg, (p < 0.01), respectively, and increased the gain by 1-2 be ats/min/mm Hg; the drugs did not influence baroreflex sensitivity to a ny significant extent in group I. The data support the hypothesis that AII can influence baroreflex sensitivity by acting at several sites i n the baroreflex are and that the direction of its effect depends on g enetic factors that predetermine the resting value of the gain of MAP/ HR relationship.