Glucocorticoids play an important role in circulatory homeostasis and in excess they cause hypertension. These corticosteroids affect the expression of many genes involved in blood pressure control including preproendothelin-1 (PPET-1), the precursor of endothelin-1 (ET-1), a potent vasoactive peptide. We have previously shown that glucocorticoids increase PPET-1 mRNA levels in rat aorta. Moreover, they also affect ETA- and ETB-receptor expression in various in vitro and in vivo situations. Both ET-1 and glucocorticoids exert direct effects in the kidney and are involved in vascular resistance and sodium balance. We therefore sought to determine the effects of glucocorticoids on renal PPET-1, ETA- and ETB-receptor expression in an animal model of glucocorticoid-induced hypertension. Wistar rats were given 2.5 mg/l of dexamethasone, a glucocorticoid agonist, in their drinking water for 1 or 5 days. Our data reveal that dexamethasone administration increases systolic blood pressure (SBP) in rats. SBP rose from 120 ± 3 to 139 ± 4 and 150 ± 5 mmHg after 1 and 5 days treatments, respectively (p < 0.05). Furthermore, dexamethasone administration decreased ETA and ETB-receptor expression in the rat kidney. This effect was observed after 1 day of dexamethasone treatment with ETA and ETB-receptor mRNA levels decreasing to 83 ± 2% and 80 ± 5% of control values, respectively (p < 0.01). Both ETA- and ETB-receptor mRNA levels further declined to 67 ± 3 and 65 ± 6% of control values after 5 days of dexamethasone treatment, respectively (p < 0.001). Interestingly, kidney PPET-1 expression was not affected by dexamethasone administration. Our results suggest a contribution of renal ET receptors in glucocorticoid actions on blood pressure control.
Division of Endocrinology, Department of Medicine, Faculty of Medicine, Université de Sherbrooke, Quebec, Canada
Address correspondence and reprint requests to Patricia Provencher, Division of Endocrinology, Department of Medicine, Université de Sherbrooke, CUSE, 3001, 12th. Avenue North, Sherbrooke, Quebec, Canada, J1H 5N4. E-mail: [email protected]
© 2000 Lippincott Williams & Wilkins, Inc.