Endothelin production in cultured mesangial cells of spontaneously hypertensive rats.
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.
Ikeda
M
M
First Department of Internal Medicine, University Medical School, Osaka City, Japan.
Kohno
M
M
Takeda
T
T
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002478:Cells, Cultured; D016232:Endothelins / Q000096:biosynthesis*; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011945:Receptors, Angiotensin / Q000502:physiology; D017483:Receptors, Vasopressin / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016232:Endothelins; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D000804:Angiotensin II; D001127:Arginine Vasopressin; C073402:PD 123319; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate