Jpn. J. Pharmacol. 79 (2), 221-229 (1999)

Long-Term Treatment With Angiotensin Converting Enzyme Inhibitor Restores Reduced Calcitonin Gene-Related Peptide-Containing Vasodilator Nerve Function in Mesenteric Artery of Spontaneously Hypertensive Rats

Hiromu Kawasaki (1), Masatoshi Okazaki (2), Akira Nakatsuma (1), Yuichi Mimaki (2), Hiroaki Araki (2) and Yutaka Gomita (2)

(1) Department of Clinical Pharmaceutical Science, Faculty of Pharmaceutical Sciences, Okayama University and (2) Department of Hospital Pharmacy, Okayama University School of Medicine, Okayama 700-8530 Japan

Abstract: Effects of long-term treatment with angiotensin converting enzyme (ACE) inhibitor on decreased function of calcitonin gene-related peptide (CGRP)-containing vasodilator nerves (CGRP nerves) in mesenteric resistance artery were investigated in spontaneously hypertensive rats (SHR). Eight-week-old SHR were treated for 7 weeks with 0.1% captopril, O.O1% temocapril, 0.05% pindolol or 0.005% hydralazine in drinking water. Long-term treatment with each drug significantly lowered mean blood pressure of SHR. In isolated and perfused mesenteric vascular beds with active tone, periarterial nerve stimulation (PNS) (0.5 to 8 Hz) produced frequency-dependent vasodilations, which were abolished by CGRP (8 - 37) (CGRP-receptor antagonist) and significantly smaller in SHR than in normotensive Wistar Kyoto rats. Treatment of SHR with captopril and temocapril but not with pindolol and hydralazine resulted in significantly greater PNS-induced vasodilation than in non-treated SHR, but ACE-inhibitor treatment did not affect vasodilation induced by exogenous CGRP. In captopril-treated SHR preparations, PNS evoked significantly larger CGRP-like immunoreactive release than in non-treated SHR. In non-treated 15-week-old SHR preparations, direct perfusion of captopril or temocapril (0.1 microM and 1 microM) did not modify frequency-dependent vasodilation in response to PNS. These results suggest that long-term ACE inhibitor treatment prevents or restores CGRP nerve function reduction in SHR.

Keywords: Angiotensin converting enzyme inhibitor, Neurogenic vasodilation, Calcitonin gene-related peptide, Spontaneously hypertensive rat, Mesenteric resistance blood vessel

Copyrightę The Japanese Pharmacological Society 1999

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