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  • Title: Endothelin production in cultured mesangial cells of spontaneously hypertensive rats.
    Author: Ikeda M, Kohno M, Takeda T.
    Journal: Hypertension; 1995 Jun; 25(6):1196-201. PubMed ID: 7768563.
    Abstract:
    Cultured glomerular mesangial cells are 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) and arginine vasopressin (AVP) is enhanced in cultured mesangial cells of spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto rats (WKY). In addition, we examined which receptor subtypes of Ang II and AVP mediate ET-1 production in these cells. 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 the SHR cells. Ang II and AVP stimulated ET-1 production in a concentration-dependent manner in mesangial cells of both rat strains, but Ang II- and AVP-induced stimulation of ET-1 production was clearly greater in SHR than WKY cells. The protein kinase C (PKC)-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 than WKY cells. Neither Ang II nor AVP stimulated ET-1 production in PKC-depleted cells of both strains. Ang II- and AVP-induced stimulation was completely abolished by selective angiotensin subtype 1 (AT1) and vasopressin subtype 1 (V1) receptor antagonists, respectively, in cells of both rat strains. These results suggest that AT1 and V1-receptor-mediated mesangial cell production of ET-1 is clearly enhanced in SHR compared with WKYs. Increased response of ET-1 production to PKC activation appears to contribute in part to the observed enhancement of ET-1 production in SHR mesangial cells.
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