Chronic angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade: Effects on cardiovascular remodeling in rats induced by the long-term blockade of nitric oxide synthesis

Masao Takemoto, Kensuke Egashira, Hideharu Tomita, Makoto Usui, Hiroshi Okamoto, Akira Kitabatake, Hiroaki Shimokawa, Katsuo Sueishi, Akira Takeshita

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Abstract

We have shown previously that angiotensin-converting enzyme (ACE) inhibitors prevent coronary vascular remodeling (medial thickening and perivascular fibrosis) and myocardial remodeling (fibrosis and hypertrophy) in rats induced by long-term inhibition of nitric oxide (NO) synthesis with oral administration of N(ω)-nitro-L-arginine methyl ester (L-NAME). ACE inhibitors inhibit both the formation of angiotensin II and the catabolism of bradykinin. In this study, we aimed to determine the relative contribution of the latter two mechanisms to the beneficial effects of an ACE inhibitor on structural remodeling. First, we examined the effects of the ACE inhibitor temocapril and the angiotensin II AT1 subtype receptor antagonist CS-866 on the structural remodeling induced by administering L-NAME for 8 weeks. Temocapril and CS-866 were equally effective in preventing remodeling. Second, we examined whether the effect of temocapril on the remodeling induced by L-NAME was reduced by the bradykinin receptor antagonist HOE140. The latter drug did not alter the beneficial effect of temocapril on remodeling. In conclusion, although species differences must be considered to apply our conclusion to clinical conditions, the present results suggest that the inhibition of angiotensin II activity, mediated via the AT1 receptors, is responsible for the beneficial effects of an ACE inhibitor in our animal model of coronary vascular and myocardial remodeling induced by the long- term inhibition of NO synthesis.

Original languageEnglish
Pages (from-to)1621-1627
Number of pages7
JournalHypertension
Volume30
Issue number6
DOIs
Publication statusPublished - Jan 1 1997

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All Science Journal Classification (ASJC) codes

  • Internal Medicine

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