(Hypertension. 1995;26:957-962.)
© 1995 American Heart Association, Inc.
Articles |
Chronic Inhibition of Nitric Oxide Synthesis Causes Coronary Microvascular Remodeling in Rats
From the Research Institute of Angiocardiology and Cardiovascular Clinic and the First Department of Pathology (K.S.), Kyushu University Faculty of Medicine, Fukuoka, Japan.
Correspondence to Kensuke Egashira, MD, PhD, The Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, 3-1-1 Higashi-ku, Fukuoka 812-82 Japan.
Abstract The aim of the present study was to investigate
the effects of long-term blockade of nitric oxide synthesis with
the L-arginine analogue
N
-nitro-L-arginine methyl
ester (L-NAME) for 8 weeks on coronary vascular and myocardial
structural changes. Four groups of Wistar-Kyoto rats were studied:
those with no treatment, those treated with L-NAME 1 g/L (3.7 mmol/L in
drinking water), those treated with L-NAME 0.1 g/L (0.37 mmol/L in
drinking water), and those treated with L-NAME 1.0 g/L and
hydralazine 120 mg/L (0.6 mmol/L in drinking water). After 8
weeks, the heart was excised, and the degrees of structural changes in
coronary arteries (wall-to-lumen ratio and perivascular
fibrosis), myocardial fibrosis, and myocyte size were quantified by an
image analyzer. Chronic inhibition of nitric oxide synthesis
increased arterial pressure compared with control animals.
Chronic inhibition of nitric oxide synthesis caused significant
microvascular remodeling (increased wall-to-lumen ratio and
perivascular fibrosis). Cardiac hypertrophy was also
observed after chronic inhibition of nitric oxide synthesis.
Coadministration of hydralazine prevented arterial
hypertension but did not affect microvascular remodeling and cardiac
hypertrophy induced by the chronic inhibition of nitric
oxide synthesis. In addition, chronic inhibition of nitric oxide
synthesis caused scattered lesions of myocardial fibrosis, which was
significantly attenuated by cotreatment with hydralazine. These
results suggest that long-term blockade of nitric oxide synthesis
caused coronary microvascular remodeling and cardiac
hypertrophy in rats in vivo by a mechanism other than
arterial hypertension. In contrast, arterial
hypertension contributed to the development of myocardial fibrosis
induced by long-term blockade of nitric oxide synthesis.
Key Words: nitric oxide • endothelium-derived relaxing factor • coronary circulation • microcirculation • cardiac hypertrophy
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