Submitted on November 7, 2005
Accepted on December 22, 2005
Effects of Chronic Cold Exposure on the Endothelin System
Gin-Fu Chen1 and Zhongjie Sun1*
1 Departments of Medicine and Physiology & Functional Genomics, University of Florida, Gainesville, FL, USA
* To whom correspondence should be addressed. E-mail: zsun{at}phys.med.ufl.edu.
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 and up-regulates ETA receptors. The aim of this study was to determine the effect of cold exposure on the regulation of the ET system. Four groups of rats (6-7 rats/group) were used. 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 (25°C) and served as control. Cold exposure significantly increased ET-1 levels in the heart, mesenteric arteries, renal cortex, and renal medulla. ETA receptor protein expressions were increased in the heart and renal cortex by cold exposure. ETB receptor expression, however, was decreased significantly in the heart and renal medulla of cold-exposed rats. Cold exposure significantly increased the ratio of ETA/ETB receptors in the heart. Additional four groups of rats (3 rats/group) were used to localize changes in ETA and ETB receptors at 1, 3, and 5 weeks after exposure to cold. Immunohistochemical analysis showed that the ETA receptor immunoreactivity was increased but the ETB receptor immunoreactivity was decreased in cardiac myocytes of cold-exposed rats. The increased ETA receptor immunoreactivity was also found in vascular smooth muscle cells (VSMC) of cold-exposed rats. Cold exposure increased ETA receptor immunoreactivity in tubule epithelial cells in the renal cortex but decreased ETB receptor immunoreactivity in tubule epithelial cells in the renal medulla. Therefore, cold exposure increased ET-1 production, up-regulated ETA receptors, and down-regulated ETB receptors.
