Selective antagonism of humoral versus neural vasoconstrictor responses by nisoldipine.

Abstract

The effects of nisoldipine [an antihypertensive-Ca+-antagonist] administration on vascular reactivity to humoral and neural vasoconstrictor stimuli were examined in the intact rat. Rats were instrumented with miniaturized pulsed Doppler flow probes to allow continuous measurement of renal, mesenteric and hindquarters blood flow. In conscious and anesthetized rats, i.v. doses of angiotensin II (75 and 150 ng/kg), norepinephrine (0.6 and 1.2 .mu.g/kg) and epinephrine (0.6 and 1.2 .mu.g/kg) caused dose-dependent increases in arterial pressure and renal and mesenteric vascular resistance. Nisoldipine (0.7 .mu.g/min) administration significantly attentuated (P < 0.05) the pressor and regional vasoconstrictor actions of all 3 circulating pressor agents; nisoldipine infusion had little effect on neurally mediated regional vasoconstrictor responses elicited by electrical stimulation of the posterior hypothalamus or greater splanchnic nerve. Nisoldipine depressed vascular responsiveness to humoral vasoconstrictor agents, while neural vasoconstrictor responses were unaffected. Thus nisoldipine appears to exert preferential antagonistic effects on humoral rather than on neural vasoconstrictor stimuli.