Abstract
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 ET(A)- and ET(B)-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, ET(A)- and ET(B)-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 ET(A) and ET(B)-receptor expression in the rat kidney. This effect was observed after 1 day of dexamethasone treatment with ET(A) and ET(B)-receptor mRNA levels decreasing to 83 +/- 2% and 80 +/- 5% of control values. respectively (p < 0.01). Both ET(A)- and ET(B)-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.
Published Version
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