title: Glucocorticoids decrease endothelin-A- and -B-receptor expression in the kidney.
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.
authors.affiliation: Department of Medicine, Faculty of Medicine, Université de Sherbrooke, Quebec, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Villeneuve
authors.forename: S
authors.initials: S
authors.lastname: Gignac
authors.forename: P H
authors.initials: PH
authors.lastname: Provencher
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D019332:Endothelin-1; D016232:Endothelins / Q000235:genetics; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000235:genetics*
chemical_list: D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D003907:Dexamethasone