title: Aldosterone does not alter endothelin B receptor signaling in the inner medullary collecting duct.
abstract: Recent studies suggest that aldosterone-mediated sulfenic acid modification of the endothelin B receptor (ETB) promotes renal injury in an ischemia/reperfusion model through reduced ETB-stimulated nitric oxide production. Similarly, aldosterone inactivation of ETB signaling promotes pulmonary artery hypertension. Consequently, we asked whether aldosterone inhibits collecting duct ETB signaling; this could promote fluid retention since CD ETB exerts natriuretic and diuretic effects. A mouse inner medullary collecting duct cell line (IMCD3) was treated with aldosterone for 48 h followed by sarafotoxin-6c, an ETB-selective agonist, and extracellular signal-related kinase 1/2 (ERK) phosphorylation assessed. S6c increased the phospho/total-ERK ratio similarly in control and aldosterone-treated cells (aldosterone alone increased phospho/total-ERK). Since cultured IMCD cell lines lack ETB inhibited AVP signaling, the effect of S6c on AVP-stimulated cAMP in acutely isolated IMCD was assessed. Rats (have much higher CD ETB expression than mice) were exposed to 3 days of a normal or low Na+diet, or low Na+diet + desoxycorticosterone acetate. S6c inhibited AVP-stimulated cAMP in rat IMCD by the same degree in the high mineralocorticoid groups compared to controls. Finally, S6c-stimulated cGMP accumulation in cultured IMCD, or S6c-stimulated nitric oxide or cGMP in acutely isolated IMCD, was not affected by prior aldosterone exposure. These findings provide evidence that aldosterone does not modify ETB effects on ERK phosphorylation, AVP-dependent cAMP inhibition, or NO/cGMP accumulation in the IMCD Thus, while aldosterone can inhibit endothelial cell ETB activity to promote hypertension and injury, this response does not appear to occur in the IMCD.
authors.affiliation: Division of Nephrology, University of Utah Health Sciences Center, Salt Lake City, Utah.|Salt Lake Veterans Affairs Medical Center, Salt Lake City, Utah.
authors.forename: Nirupama
authors.initials: N
authors.lastname: Ramkumar
authors.affiliation: Division of Nephrology, University of Utah Health Sciences Center, Salt Lake City, Utah.|Salt Lake Veterans Affairs Medical Center, Salt Lake City, Utah.
authors.forename: Deborah
authors.initials: D
authors.lastname: Stuart
authors.affiliation: Division of Nephrology, University of Utah Health Sciences Center, Salt Lake City, Utah.|Salt Lake Veterans Affairs Medical Center, Salt Lake City, Utah.
authors.forename: Tianxin
authors.initials: T
authors.lastname: Yang
authors.affiliation: Division of Nephrology, University of Utah Health Sciences Center, Salt Lake City, Utah donald.kohan@hsc.utah.edu.|Salt Lake Veterans Affairs Medical Center, Salt Lake City, Utah.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Kohan
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D007679:Kidney Medulla / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D044023:Receptor, Endothelin B / Q000378:metabolism*; D014757:Viper Venoms / Q000494:pharmacology
chemical_list: D044023:Receptor, Endothelin B; D014757:Viper Venoms; C057354:sarafotoxins s6; D009569:Nitric Oxide; D000450:Aldosterone; D000242:Cyclic AMP; D006152:Cyclic GMP
keywords: Aldosterone; collecting duct; endothelin; endothelin B receptor; signaling