Chronic Exposure to Carbon Monoxide and Nicotine: Endothelin ETA Receptor Antagonism Attenuates Carbon Monoxide-Induced Myocardial Hypertrophy in Rat
| Autor: | Ingerid Arbo, Petter Aadahl, Odd G. Nilsen, Arne K. Sandvik, Turid Nilsen, Helge L. Waldum, Øyvind Ellingsen, Jan Pål Loennechen |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Endothelin Receptor Antagonists
Atmosphere Exposure Chambers Nicotine medicine.medical_specialty Cardiomegaly Toxicology Left ventricular hypertrophy Muscle hypertrophy Rats Sprague-Dawley chemistry.chemical_compound Atrial natriuretic peptide Right ventricular hypertrophy Internal medicine medicine Animals Nicotinic Agonists RNA Messenger Pharmacology Carbon Monoxide Endothelin-1 Phenylpropionates Body Weight Organ Size Receptor Endothelin A medicine.disease Rats Pyrimidines Endocrinology chemistry Carboxyhemoglobin cardiovascular system Female Antagonism Endothelin receptor Atrial Natriuretic Factor medicine.drug |
| Zdroj: | Toxicology and Applied Pharmacology. 178:8-14 |
| ISSN: | 0041-008X |
| Popis: | The aims of the present study were to determine the effects of endothelin ET(A) 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 microg/m3), or air for 14 consecutive days. In each exposure group, animals were randomized to ET(A) 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). ET(A) 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 ET(A) receptor antagonism reduces right ventricular hypertrophy induced by chronic CO exposure, whereas CO-induced myocardial ET-1 expression remains unchanged. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect