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.