title: Chronic exposure to carbon monoxide and nicotine: endothelin ET(A) receptor antagonism attenuates carbon monoxide-induced myocardial hypertrophy in rat.
abstract: 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.
authors.affiliation: Department of Physiology and Biomedical Engineering, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Jan P
authors.initials: JP
authors.lastname: Loennechen
authors.forename: Odd G
authors.initials: OG
authors.lastname: Nilsen
authors.forename: Ingerid
authors.initials: I
authors.lastname: Arbo
authors.forename: Petter
authors.initials: P
authors.lastname: Aadahl
authors.forename: Turid
authors.initials: T
authors.lastname: Nilsen
authors.forename: Helge L
authors.initials: HL
authors.lastname: Waldum
authors.forename: Arne K
authors.initials: AK
authors.lastname: Sandvik
authors.forename: O
authors.initials: O
authors.lastname: Ellingsen
mesh_terms: D000818:Animals; D001273:Atmosphere Exposure Chambers; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis; D001835:Body Weight / Q000187:drug effects; D002248:Carbon Monoxide / Q000097:blood / Q000633:toxicity*; D006332:Cardiomegaly / Q000139:chemically induced* / Q000517:prevention & control*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000096:biosynthesis; D005260:Female; D009538:Nicotine / Q000097:blood / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000097:blood / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D010666:Phenylpropionates / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D018722:Nicotinic Agonists; D010666:Phenylpropionates; D011743:Pyrimidines; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; C107831:darusentan; D009538:Nicotine; D002248:Carbon Monoxide; D009320:Atrial Natriuretic Factor