Regular Article
Chronic Exposure to Carbon Monoxide and Nicotine: Endothelin ETA Receptor Antagonism Attenuates Carbon Monoxide-Induced Myocardial Hypertrophy in Rat

https://doi.org/10.1006/taap.2001.9300Get rights and content

Abstract

The aims of the present study were to determine the effects of endothelin ETA receptor antagonism on carbon monoxide (CO)-induced cardiac hypertrophy and endothelin-1 (ET-1) expression and to compare myocardial effects of chronic nicotine with CO exposure. Female Sprague–Dawley rats (n = 84) were randomized to three groups exposed 20 h/day to CO (200 ppm), nicotine (500 μg/m3), or air for 14 consecutive days. In each exposure group, animals were randomized to ETA receptor antagonist LU 135252 in drinking water (0.5 mg/ml) or placebo. Myocardial ET-1 and atrial natriuretic peptide (ANP) expression was measured by competitive RT–PCR and plasma ET-1 by immunoassay. Carboxyhemoglobin was 22.1 ± 0.3% in CO-exposed animals and 2.8 ± 0.3% in controls. Plasma nicotine was 57 ± 7 ng/ml and plasma cotinine was 590 ± 23 ng/ml in nicotine-exposed animals and below detection levels in controls. CO exposure induced a 21% increase in right ventricular hypertrophy (p < 0.01), a 7% increase in left ventricular hypertrophy (p < 0.01), a 25% increase in right ventricular ET-1 expression (p < 0.05), and an eightfold increase in ANP expression (p = 0.08). ETA receptor antagonism reduced right ventricular hypertrophy by 60% (p < 0.05) with no significant effect on left ventricular hypertrophy or myocardial ET-1 expression. Chronic nicotine exposure did not significantly affect cardiac weights or ANP and ET-1 expression. We conclude that ETA receptor antagonism reduces right ventricular hypertrophy induced by chronic CO exposure, whereas CO-induced myocardial ET-1 expression remains unchanged.

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