Glucocorticoids decrease endothelin-A- and -B-receptor expression in the kidney

Glucocorticoids play an important role in circulatory homeostasis and in ex cess they cause hypertension. These corticosteroids affect the expression o f many genes involved in blood pressure control including preproendothelin- 1 (PPET-1), the precursor of endothelin-1 (ET-1), a potent vasoactive pepti de. We have previously shown that glucocorticoids increase PPET-1 mRNA leve ls in rat aorta. Moreover, they also affect ETA- and ETB-receptor expressio n 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 glucoc orticoids on renal PPET-1, ETA- and ETB-receptor expression in an animal mo del 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 syst olic blood pressure (SBP) in rats. SEP rose from 120 +/- 3 to 139 +/- 4 and 150 +/- 5 mmHg after 1 and 5 days treatments, respectively (p < 0.05). Fur thermore, dexamethasone administration decreased ETA and ETB-receptor expre ssion in the rat kidney. This effect was observed after 1 day of dexamethas one treatment with ETA and ETB-receptor mRNA levels decreasing to 83 +/- 24 6 and 80 +/- 5% of control values, respectively (p < 0.01). Both ETA- and E TB-receptor mRNA levels further declined to 67 +/- 3 and 65 +/- 6% of contr ol values after 5 days of dexamethasone treatment, respectively (p<0.001). Interestingly, kidney PPET-1 expression was not affected by dexamethasone a dministration. Our results suggest a contribution of renal ET receptors in glucocorticoid actions on blood pressure control.