Endothelin Production in Cultured Mesangial Cells of Spontaneously Hypertensive Rats

Abstract

Abstract Cultured glomerular mesangial cells have been shown to produce a potent vasoconstrictive peptide, endothelin-1 (ET-1). We examined whether basal or stimulated ET-1 production by angiotensin II (Ang II) or arginine vasopressin (AVP) is enhanced in cultured mesangial cells of spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto rats (WKY). Basal ET-1 production in SHR mesangial cells was not different from that in WKY cells although a trend toward increased ET-1 production was observed in SHR cells. Ang II and AVP stimulated ET-1 production in a concentration-dependent manner in cells of both rat strains, but the agonist-induced stimulation was clearly greater in SHR cells than WKY cells. The protein kinase C–activating phorbol ester phorbol myristate acetate stimulated ET-1 production in a concentration-dependent manner in cells of both rat strains, but this stimulation was significantly greater in SHR cells than in WKY cells. These results suggest that Ang II– and AVP-induced mesangial cell production of ET-1 is clearly enhanced in SHR compared with WKY. Increased response of ET-1 production to protein kinase C activation appears to contribute in part to the observed enhancement of ET-1 production in SHR mesangial cells.