Chronic inhibition of nitric oxide synthesis reverses the effects
of ace inhibition on neo-endothelium-dependent relaxation and on
intimal thickening after balloon injury.
Belle, Eric Van, Beno[circumflex]it Vallet, Jean-Luc Auffray,
Christophe Bauters, Martial Hamon, Eug[grave]ene P. Mc Fadden, Jean
-Marc Lablanche, Bernard Dupuis, Michel E. Bertrand.
Departments of Cardiology and Pharmacology, University of Lille,
59037 Lille Cedex, France
APStracts 2:0310H, 1995.
Angiotensin Converting enzyme (ACE) inhibitors reduce intimal
hyperplasia after balloon injury. A role for nitric oxide (NO) has
been suggested in this effect. As recent data suggest that NO may
modulate some features of endothelial cells and as 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 neo-endothelial dysfunction and on intimal
hyperplasia in a rabbit model of unilateral iliac balloon injury.
New-Zealand male rabbits received placebo, perindopril or co
-treatment with perindopril and N-nitro-L-arginine-methyl-ester (L
-NAME) and were evaluated four weeks after the injury. Fifteen rabbits
(5 each group) were used to assess in vitro vasoreactivity and 24 (8
in each group) for morphometric analysis. In injured vessels, neo
-endothelium-dependent relaxation in ACE inhibitor treated animals was
improved compared to placebo (P < 0.05) and restored to the
level of non-injured 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 neo-endothelium
-independent vasoreactivity. The improved neo-endothelial dysfunction
with ACE inhibitor was associated with a 66% reduction in intimal
thickening (P < 0.01). This effect was also reversed by co
-treatment with L-NAME (P < 0.01). In non-injured 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.
Received 3 February 1995; accepted in final form 7 July 1995.
APS Manuscript Number H99-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 July 1995.