Reduction of blood pressure variability by amlodipine in baroreceptor denervated rats

To determine the effect of the calcium blocker amlodipine on the variabilit y of mean arterial pressure (MAP), amlodipine besylate was acutely administ ered to sine-aortic baroreceptor-denervated (SAD) rats (0, 1, 3, 10 mg/kg s .c.), and chronically administered to SAD and sham-denervated rats (0, 50, 150, 500, and 1500 mg kg(-1) feed, 4 days per dose). Acute amlodipine admin istration caused significant dose-dependent reductions of the mean MAP leve l and short-term MAP variability at the 3 and 10 mg/kg dose levels, respect ively. Chronic administration produced dose-dependent reductions in short-t erm MAP variability, becoming significant at the 150 and 500 mg kg(-1) feed dose level in SAD and Sham groups, respectively. Day-night differences in blood pressure were significantly attenuated or reversed at the 500 and 150 0 mg kg(-1) feed dose levels. Amlodipine had little or no effect upon the 2 4 h MAP level, long-term MAP variability, and only modestly reduced the MAP response to hexamethonium. These results demonstrate that amlodipine can r educe MAP variability independent of changes in the mean blood pressure lev el.