Important role of tissue angiotensin-converting enzyme activity in the pathogenesis of coronary vascular and myocardial structural changes induced by long-term blockade of nitric oxide synthesis in rats

Masao Takemoto, Kensuke Egashira, Makoto Usui, Kohtaro Numaguchi, Hideharu Tomita, Hiroyuki Tsutsui, Hiroaki Shimokawa, Katsuo Sueishi, Akira Takeshita

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307 Citations (Scopus)

Abstract

The long-term administration of N(ω)-nitro-L-arginine methyl ester (L- NAME), an inhibitor of nitric oxide synthesis, produces coronary vascular remodeling and myocardial hypertrophy in animals. This study used a rat model to investigate the role of angiotensin I converting enzyme (ACE) in the pathogenesis of such changes. We studied the following groups, all of which received drug treatment in their drinking water: untreated controls, and those administered L-NAME, L-NAME, and an ACE inhibitor (ACEI), and L-NAME and hydralazine. Cardiovascular structural changes and tissue ACE activities were evaluated after the first, fourth, and eighth week of treatment. In rats treated with L-NAME alone, vascular remodeling was evident at the fourth and eighth week, and myocardial hypertrophy was present at the eighth week of treatment. The vascular and myocardial remodeling were characterized by increased tissue ACE activities and immunodetectable ACE in those tissues. These changes were markedly reduced by ACEI, but not by hydralazine treatment. Increased local ACE expression may thus be important in the pathogenesis of cardiovascular remodeling in this model.

Original languageEnglish
Pages (from-to)278-287
Number of pages10
JournalJournal of Clinical Investigation
Volume99
Issue number2
DOIs
Publication statusPublished - Jan 15 1997

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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