Chronic Cold Exposure Activates the Endothelin System

Cold temperatures have adverse effects on the human cardiovascular system. Endothelin‐1 (ET‐1) is a potent vasoconstrictor. We hypothesized that cold exposure increases ET‐1 production, up‐regulates ET A receptors, and down‐regulates ET B receptors. The aim of this study was to determine the effect of cold exposure on the regulation of the ET system. Experiment #1 used four groups of rats (6–7/group). Three groups were exposed to moderate cold (6.7±2°C) for 1, 3, and 5 weeks, respectively, while the remaining group was kept at room temperature (24°C) and served as control. Cold exposure significantly increased ET‐1 levels in the heart, small rteries, renal cortex, and renal medulla. ET A receptor mRNA and protein expressions were increased in the heart and renal cortex by cold exposure. ET B receptor expression, however, was decreased significantly in the heart and renal medulla of cold‐exposed rats. Cold exposure significantly increased the ratio of ET A /ET B receptors in the heart. Experiment #2 used four groups of rats (3/group) to localize changes in ET A and ET B receptors at 1, 3, and 5 weeks after exposure to cold. Immunohistochemical analysis showed that ET A receptor expression was increased but ET B receptor expression was decreased in the heart of cold‐exposed rats. Cold exposure increased ET A receptor expression in tubules and glomerular vascular smooth muscle cells (VSMC) in the renal cortex but decreased ET B receptor expression in tubule epithelial cells in the renal medulla. Therefore, cold exposure increased ET‐1 production, up‐regulated ET A receptors, and down‐regulated ET B receptors. These results suggest that chronic cold exposure activates the ET system.