Effects of Long-Term Treatment With Calcium Antagonists on Periarterial Nerve Function in the Mesenteric Artery of Spontaneously Hypertensive Rats

Abstract

The effect of long−term treatment with dihydropyridine calcium antagonists(amlodipine, pranidipine, nicardipine)on the periarterial nerve function was investigated in the perfused mesenteric vascular bed isolated from spontaneously hypertensive rat(SHR).Male 8−week−old SHR received amlodipine(0.01% and 0.02%)and nicardipine(0.1%)in drinking water and pranidipine(0.0035% and 0.035%)in rat chow for 7 weeks.Mean blood pressure in SHR was significantly lowered by long−term treatment with each calcium antagonist.In mesenteric vascular preparations treated with each calcium antagonist, vasoconstriction induced by periarterial nerve stimulation(PNS;4, 8 and 12 Hz)was significantly smaller than that in non−treated SHR.The PNS(8 Hz)−evoked norepinephrine(NE)overflow in the perfusate was significantly decreased by amlodipine and pranidipine treatment, whereas nicardipine−treatment significantly enhanced the overflow of NE.In preparations with active tone produced by methoxamine and guanethidine, the PNS−induced vasodilation mediated by calcitonin gene−related peptide(CGRP)−containing(CGRPergic)vasodilator nerves was not affected by these drugs.These results suggest that long−term treatment of SHR with long−acting drugs, amlodipine and pranidipine, reduces sympathetic adrenergic nerve function but calcium antagonists have no effect on CGRPergic nerve function.