Denan Jin, Shinji Takai, Mayumi Yamada, Masato Sakaguchi and Mizuo Miyazaki*
Department of Pharmacology, Osaka Medical College, 2-7 Daigaku-machi,
Takatsuki City, Osaka 569-8686, Japan
*Corresponding author.ÊÊFax:+81-726-84-6518
E-mail: pha001@art.osaka-med.ac.jp
Abstract: Recently, a chymase-dependent angiotensin (Ang)ÊII-forming
pathway was found in human cardiovascular tissues, and the significance
of this pathway in the pathogenesis of some cardiovascular diseases was
suggested. The present study examined the ratio of angiotensin converting
enzyme (ACE) to chymase-dependent AngÊII formation in various isolated vessels
from monkeys, dogs and rats. In all of the examined vessels, the addition
of KCl at a concentration of 50ÊmM could induce a maximal contraction. Except
for monkey coronary artery and rat renal and femoral artery, the addition
of AngÊI could induce transitory contractions, whereas the force of contractions
in these vessels was quite different. The sensitivity to AngÊII in these
vessels was similar to that for AngÊI. In monkey gastroepiploic and mesenteric
arteries, about 70% of the AngÊI-induced contraction was suppressed by chymase
inhibition, while it was suppressed about 50% in monkey renal, femoral and
carotid arteries. In dog renal arteries, about 65% of the AngÊI-induced
contraction was suppressed by chymase inhibition, while it was suppressed
by about 30% in other dog arteries. In contrast, in all rat arteries, AngÊI-induced
contractions were completely suppressed by treatment with ACE inhibitor
alone. We concluded that regional differences in the response to AngÊI exist
in vascular tissues, and the ratio of ACE- to chymase-dependent AngÊII formation
is different in the various vessels.
Keywords: Chymase, Angiotensin converting enzyme, AngiotensinÊI, Regional
difference, Smooth muscle
Copyright© The Japanese Pharmacological Society 2000
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