Chronic carbon monoxide exposure in vivo induces myocardial endothelin-1 expression and hypertrophy in rat.
Smoking is associated with endothelial dysfunction and increased plasma levels of endothelin-1. The component of tobacco smoke inducing these effects is unknown. Carbon monoxide induces hypoxia, and there is evidence of carbon monoxide acting as a local mediator in both endothelial and smooth muscle cells. The purpose of this study was to determine whether chronic carbon monoxide exposure similar to that experienced by smokers affects myocardial endothelin-1 expression. Sprague-Dawley female rats were exposed to carbon monoxide 100 ppm for one week or to 100 ppm for one week and 200 ppm for a second week. Carboxyhaemoglobin was 12+/-0.9% in the low and 23+/-1.1% in the high carbon monoxide exposure group. Endothelin-1 expression was measured by competitive reverse transcriptase polymerase chain reaction. High carbon monoxide exposure increased endothelin-1 mRNA by 54+/-12% (P<0.001) in the left ventricle and by 53+/-12% (P<0.001) in the right ventricle. In the low carbon monoxide exposure group corresponding changes were 43+/-14% (P=0.06) and 12+/-16%(P=0.29). Right ventricular weight increased by 18+/-7% (P=0.02) after high and by 16+/-5% (P=0.02) after low exposure. Left ventricular weight was elevated by 5+/-2% (P=0.05) when both exposure groups were compared to controls. We conclude that chronic carbon monoxide exposure leading to carboxyhaemoglobin levels similar to those observed in smokers increases endothelin-1 gene expression and induces myocardial hypertrophy in the rat.
Loennechen
J P
JP
Department of Physiology and Biomedical Engineering, Norwegian University of Science and Technology, Trondheim.
Beisvag
V
V
Arbo
I
I
Waldum
H L
HL
Sandvik
A K
AK
Knardahl
S
S
Ellingsen
O
O
D000818:Animals; D002248:Carbon Monoxide / Q000633:toxicity*; D002263:Carboxyhemoglobin / Q000187:drug effects; D006332:Cardiomegaly / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019332:Endothelin-1; D012333:RNA, Messenger; D002248:Carbon Monoxide; D002263:Carboxyhemoglobin