Chronically administered
N(omega)nitro-L-arginine methyl ester (
L-NAME) produces vascular structural changes and
fibrosis of the left ventricle (LV). However, very few studies have evaluated whether the beneficial effects of
angiotensin-converting enzyme (
ACE) inhibitors on these myocardial remodelings are associated with local gene expression of
nitric oxide synthase (NOS) and ACE
mRNA in the LV. Effects of long term treatment with
imidapril, an
ACE inhibitor, on gene expression of endothelial-cell NOS (eNOS) and ACE
mRNA in the LV and its relation to myocardial remodeling in
L-NAME-induced hypertensive rats were evaluated. Fifteen male Sprague-Dawley rats were given
L-NAME (60 mg/ kg/day) in
drinking water for 6 weeks to induce
hypertension, and then treated with
imidapril (
L-NAME-I, n = 8, 1 mg/kg/day, subdepressor dose), or a vehicle (
L-NAME-V, n = 7) for 4 weeks. Age-matched rats (C, n = 7) served as a control group. Blood pressure in
L-NAME-V and
L-NAME-I was similar and significantly higher than that in C. The level of eNOS
mRNA in the LV was significantly decreased in
L-NAME-V compared with C, and was significantly increased in
L-NAME-I compared with C and
L-NAME-V. The ACE
mRNA and
type I collagen mRNA expression levels were significantly increased in
L-NAME-V compared with C, and significantly suppressed in
L-NAME-I compared with
L-NAME-V.
L-NAME-V demonstrated a significant increase in wall-to-lumen ratio, perivascular
fibrosis, and myocardial
fibrosis. These changes in the microvasculature were improved significantly by
imidapril. Myocardial remodeling in
L-NAME-induced hypertensive rats was significantly ameliorated by a subdepressor dose of
imidapril, which may be due to an increase in local eNOS
mRNA expression and a decrease in
angiotensin II in the LV.