Analysis of the action of angiotensin II on the baroreflex control of heart rate in conscious rabbits

Abstract

There is considerable evidence that angiotensin II (Ang II) attenuates the baroreflex control of heart rate (HR), but the mechanism and site of this action have not been precisely defined. In the present study the effects of systemically and centrally administered Ang II on the baroreflex control of HR were investigated in conscious, chronically prepared rabbits. Baroreflex curves (HR vs. mean arterial pressure) were generated with iv infusions of phenylephrine or nitroprusside. Background infusion of Ang II at 10 ng/kg.min increased mean arterial pressure from 77.3 +/- 3.0 to 94.3 +/- 4.1 mm Hg (P less than 0.001) without changing HR [212.1 +/- 7.2 to 218.0 +/- 9.8 beats/min (bpm)] and shifted (reset) the baroreflex curve with phenylephrine to a higher pressure level (P less than 0.001) without changing its slope (-1.40 +/- 0.40 to -1.65 +/- 0.46 bpm/mm Hg; P = 0.4). Background infusion of an equipressor dose of phenylephrine did not shift the baroreflex curve or change its slope. Ang II also shifted the baroreflex curve with nitroprusside to a higher pressure level (P less than 0.01), but again the slope was not significantly changed (-2.30 +/- 1.25 to -1.51 +/- 0.52 bpm/mm Hg; P = 0.2). Background intraventricular infusion of Ang II at 1 ng/kg.min had the same effects as iv infusion of Ang II at 10 ng/kg.min; the curve was shifted to a higher pressure level (P less than 0.001), but the slope was not changed (-0.76 +/- 0.47 to -1.143 +/- 0.48 bpm/mm Hg). Intravenous infusion of Ang II at 1 ng/kg.min had no effect on the baroreflex. The resetting of the baroreflex with phenylephrine by iv Ang II (10 ng/kg.min) was not blocked by propranolol: atropine markedly reduced the baroreflex response to phenylephrine in both the absence and presence of Ang II. These results indicate that in conscious rabbits, Ang II resets the baroreflex control of HR, but does not change its sensitivity. This effect apparently results from an action of Ang II on the brain that is mediated by withdrawal of vagal tone to the heart. The resetting of the baroreflex by Ang II can explain the ability of the peptide to increase arterial pressure without decreasing HR.