Jpn. J. Pharmacol. 84 (4), 449-454 (2000)

The Functional Ratio of Chymase and Angiotensin Converting Enzyme in Angiotensin I-Induced Vascular Contraction in Monkeys, Dogs and Rats

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.╩╩Fax:+81-726-84-6518

Abstract: Recently, a chymase-dependent angiotensin (Ang)╩II-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 Ang╩II formation in various isolated vessels from monkeys, dogs and rats. In all of the examined vessels, the addition of KCl at a concentration of 50╩mM could induce a maximal contraction. Except for monkey coronary artery and rat renal and femoral artery, the addition of Ang╩I could induce transitory contractions, whereas the force of contractions in these vessels was quite different. The sensitivity to Ang╩II in these vessels was similar to that for Ang╩I. In monkey gastroepiploic and mesenteric arteries, about 70% of the Ang╩I-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 Ang╩I-induced contraction was suppressed by chymase inhibition, while it was suppressed by about 30% in other dog arteries. In contrast, in all rat arteries, Ang╩I-induced contractions were completely suppressed by treatment with ACE inhibitor alone. We concluded that regional differences in the response to Ang╩I exist in vascular tissues, and the ratio of ACE- to chymase-dependent Ang╩II formation is different in the various vessels.

Keywords: Chymase, Angiotensin converting enzyme, Angiotensin╩I, Regional difference, Smooth muscle

Copyrightę The Japanese Pharmacological Society 2000

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