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 losartan given by acute intravenous (i.v.) injection, on cardiac baroreflex sensitivity in two groups of conscious normotensive rabbits bred for high 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 μg/kg) and nitro-glycerin (NTG 1-20 μg/kg) after pretreatment with saline or with All, enalapril. or losartan. In group II, All had a biphasic effect on baroreflex sensitivity; at 10 and 50 μg/kg/min, it increased the gain from 3.47 ± 0.21 to 4.75 ± 0.44 and 5.13 ± 0.28 beats/min/mm Hg (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, All 50 ng/kg/min increased BP by 8 mm Hg, (p < 0.05) and decreased gain from 6.13 ± 0.32 to 4.75 ± 0.44 beats/min/mm Hg (p < 0.01). Therefore, All 50 ng/kg/min equalized baroreflex sensitivity in the two groups. In group II, both losartan (2.5 mg/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 beats/min/mm Hg; the drugs did not influence baroreflex sensitivity to any significant extent in group I. The data support the hypothesis that All can influence baroreflex sensitivity by acting at several sites in the baroreflex arc and that the direction of its effect depends on genetic factors that predetermine the resting value of the gain of MAP/HR relationship.