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(Hypertension. 1995;25:1196-1201.)
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Articles

Endothelin Production in Cultured Mesangial Cells of Spontaneously Hypertensive Rats

Miwako Ikeda; Masakazu Kohno; Tadanao Takeda

From the First Department of Internal Medicine, Osaka City (Japan) University Medical School.

Correspondence to Miwako Ikeda, MD, Division of Hypertension and Atherosclerosis, First Department of Internal Medicine, Osaka City University Medical School, 1-5-7 Asahi-machi, Abeno-ku, Osaka 545, Japan.

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.

Key Words: angiotensin II • arginine vasopressin • endothelin • mesangial cells • rats, inbred SHR • protein kinase C • rats, inbred WKY

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