Abstract

High doses of the Ca++-channel blocker nifedipine reduce blood pressure variability (BPV) at low (LF, 0.02-0.2 Hz) and mid frequencies (MF, 0.2-0.6 Hz) in rats. We tested the hypothesis that these effects are due to inhibition of myogenic vascular function and reduced vascular sympathetic responsiveness, respectively. Normotensive Wistar Kyoto rats were instrumented with catheters in the femoral artery and vein. After 24 h of recovery, blood pressure and heart rate were recorded in conscious rats during baseline conditions and i.v. infusion of nifedipine at 6 doses (0.05 mg/kg/h to 25.0 mg/kg/h). Nifedipine caused a dose-dependent decrease in blood pressure and increase in heart rate. Increasing doses of nifedipine gradually decreased LF BPV from 55.2±5.4 % during baseline conditions to 30.3±5.8 % at 25 mg/kg/h (P<0.05). In contrast, relative MF BPV increased from 19.9±4.0 % at baseline conditions to 27.0±3.1 % at a dose of 0.5 mg/kg/h (P<0.05) and then declined to 12.3±2.1 % at 25 mg/kg/h. At low doses of nifedipine (0.5 mg/kg/h), MF BPV increased most likely due to baroreflex activation of sympathetic nerve activity. At higher doses, MF BPV declined probably due to reduced vascular sympathetic responsiveness. The lack of an increase in LF BPV at low doses of nifedipine indicates that sympathetic modulation of vascular tone does not affect LF BPV. Instead, inhibition of myogenic vascular function may explain the decrease in LF BPV with increasing doses of nifedipine. These results suggest that myogenic vascular function is exclusively reflected in LF BPV, while sympathetic modulation of vascular tone is exclusively reflected in MF BPV.

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