Influecne of nifedipine on arterial baroreflex modulation of heart rate control during dynamic increases in arterial pressure: Studies in normal man

Abstract

Studies in animals have demonstrated that calcium channel blocking agents exert important influences on autonomic mechanisms in addition to their direct vascular effects. Previous studies in our laboratory showed that clinical doses of nifedipine sensitized baroreceptor-mediated control of peripheral vascular resistance in normal human subjects. However, baroreflex control of vascular tone does not necessarily imply parallel control of heart rate. A series of experiments was therefore performed to test the hypothesis that therapeutic doses of nifedipine would potentiate arterial baroreflex modulation of heart rate during ramp increases of arterial pressure in normal volunteers. Arterial baroreflex control was assessed by measuring heart interval (HI) responses to dynamic ramp elevation of systolic arterial pressure (SAP) with bolus administration of phenylephrine (PE) before and after nifedipine or placebo in 19 normal subjects. Arterial baroreflex control was calculated from the slope of the regression of SAP on succeeding HI during the first 18 cardiac cycles following onset of rise of SAP after PE bolus. In 13 subjects, bolus PE produced an increase in SAP from 125 ± 3 mm Hg to 152 ± 5 mm Hg ( p < 0.01), with a resultant increase in HI from 1110 ± 57 msec to 1541 ± 87 msec ( p < 0.01). The baroreflex response was linear ( r > 0.80, p < 0.025) and = 17.8 ± 3.3 msec/mm Hg. After nifedipine (20 mg sublingual), there was no change in central venous pressure and the same dose of PE increased SAP from a similar baseline value of 119 ± 3 mm Hg ( p = NS vs pre nifedipine) to 133 ± 3 mm Hg ( p < 0.01), with a consequent increase in HI from 957 ± 41 msec to 1254 ± 64 msec ( p < 0.01). The baroreflex slope of this response post nifedipine was augmented to 22.5 ± 2.8 msec/mm Hg ( p < 0.05 pre vs post nifedipine). In six additional subjects, administration of placebo had no effect on arterial baroreflex responses to PE-induced increase in SAP. Thus, in addition to augmenting baroreceptor modulation of vascular resistance in normal man, nifedipine also augments arterial baroreceptor modulation of heart rate during dynamic elevations of arterial pressure.