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.ﾊﾊFAX:+81-86-251-7970
E-mail: kawasaki@pheasant.pharm.okayama-u.ac.jp
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ﾊ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ﾊHz) was significantly smaller than that in
non-treated SHR. The PNS (8ﾊ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ｩ The Japanese Pharmacological Society 2000
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