Chronic carbon monoxide exposure in vivo induces myocardial endothelin-1 expression and hypertrophy in rat

Smoking is associated with endothelial dysfunction and increased plasma lev els of endothelin-l. The component of tobacco smoke inducing these effects is unknown. Carbon manoxide induces hypoxia, and there is evidence of carbo n monoxide acting as a local mediator in both endothelial and smooth muscle cells. The purpose of this study was to determine whether chronic carbon m onoxide exposure similar to that experienced by smokers affects myocardial endothelin-l 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 t he high carbon monoxide exposure group. Endothelin-l expression was measure d by competitive reverse transcriptase polymerase chain reaction. High carb on monoxide exposure increased endothelin-l mRNA by 54+/-12% (P<0.001) in t he 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 ventric ular weight was elevated by 5+/-2% (P = 0.05) when both exposure groups wer e compared to controls. We conclude that chronic carbon monoxide exposure l eading to carboxyhaemoglobin levels similar to those observed in smokers in creases endothelin-l gene expression and induces myocardial hypertrophy in the rat.