Jpn. J. Pharmacol. 84 (2), 156-162 (2000)

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

Akira Nakatsuma1, Hiromu Kawasaki1,*, Yuji Kurosaki1, Kojiro Futagami2, Hiroaki Araki2 and Yutaka Gomita2

1Department of Clinical Pharmaceutical Science, Graduate School of Natural Science and Technology, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan
2Department of Hospital Pharmacy, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
*Corresponding author.  FAX:+81-86-251-7970

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.

Keywords: Calcium antagonist, Adrenergic vasoconstrictor nerve, Calcium gene-related peptide-containing vasodilator nerve, Spontaneously hypertensive rat, Mesenteric artery

Copyright© The Japanese Pharmacological Society 2000

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