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