NO synthesis is involved in structural and functional effects of ACE inhibitors in injured arteries.

Abstract

Angiotensin-converting enzyme (ACE) inhibitors reduce intimal hyperplasia after balloon injury. A role for nitric oxide (NO) has been suggested in this effect. Because recent data suggest that NO may modulate some features of endothelial cells and because endothelial cells are involved in the control of intimal hyperplasia, we investigated the role of NO synthesis in the effect of an ACE inhibitor, perindopril, on neoendothelial dysfunction and intimal hyperplasia in a rabbit model of unilateral iliac balloon injury. New Zealand White male rabbits received placebo, perindopril, or cotreatment with perindopril and NG-nitro-L-arginine methyl ester (L-NAME) and were evaluated 4 wk after the injury. Fifteen rabbits (5 in each group) were used to assess in vitro vasoreactivity and twenty-four (8 in each group) for morphometric analysis. In injured vessels, neoendothelium-dependent relaxation in ACE inhibitor-treated animals was improved compared with placebo (P < 0.05) and restored to the level of noninjured vessels (NS). The improvement observed with ACE inhibitor was abolished by cotreatment with L-NAME (P < 0.05). In the same vessels, no effect was observed on neoendothelium-independent vasoreactivity. The improved neoendothelial dysfunction with ACE inhibitor was associated with a 66% reduction in intimal thickening (P < 0.01). The effect was also reversed by cotreatment with L-NAME (P < 0.01). In noninjured vessels, treatment did not alter vasoreactivity or morphology of the vessel wall. These results suggest that NO synthesis may play a key role in the improvement of vascular function seen with ACE inhibitor in balloon-injured vessels.