Reduction of Blood Pressure Variability by Amlodipine in Baroreceptor Denervated Rats

To determine the effect of the calcium blocker amlodipine on the variability of mean arterial pressure (MAP), amlodipine besylate was acutely administered to sino-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 1,500 mg x kg(-1) feed, 4 days per dose). Acute amlodipine administration caused significant dose-dependent reductions of the mean MAP level and short-term MAP variability at the 3 and 10 mg/kg dose levels, respectively. Chronic administration produced dose-dependent reductions in short-term MAP variability, becoming significant at the 150 and 500 mg x 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 1,500 mg x kg(-1) feed dose levels. Amlodipine had little or no effect upon the 24 h MAP level, long-term MAP variability, and only modestly reduced the MAP response to hexamethonium. These results demonstrate that amlodipine can reduce MAP variability independent of changes in the mean blood pressure level.