Role of protein kinase C in renal vasoconstriction caused by angiotensin II.
In this study we have examined the subcellar pathways along which angiotensin II (ANG II) causes renal vasoconstriction. Using the isolated perfused rat kidney model, we found that renal vasoconstriction produced by ANG II (100 pM) was not altered by the calmodulin antagonists calmidazolium (1 microM) and N-(6-aminohexyl)-5-chloro-1-naphthalensulfonamide (W-7, 10 microM) but was blunted by staurosporine (100 nM) and 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H-7, 50 microM), two structurally distinct putative protein kinase C inhibitors. The phorbol ester 4 alpha-phorbol 12,13-didecanoate (1-100 nM) did not alter renal vascular resistance, whereas phorbol 12-myristate 13-acetate (PMA, 1-100 nM) caused potent and dose-dependent vasoconstriction that was prevented by staurosporine (100 nM) and H-7 (50 microM). The vasoconstrictory effects of ANG II and PMA were attenuated by the calcium channel blockers verapamil (5 microM) and nifedipine (5 microM) and were reversibly inhibited when cobaltous chloride (2 mM) was added to the perfusate. Taken together, our findings support the concept that the renal vasoconstrictory effect of ANG II is essentially mediated by protein kinase C activation, which either requires or enhances the entrance of extracellular calcium.
Physiologisches Institut, Universität Zürich, Switzerland.
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D003035:Cobalt / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects*; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D000470:Alkaloids; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007546:Isoquinolines; D010879:Piperazines; D000804:Angiotensin II; D003035:Cobalt; C031938:calmidazolium; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D014700:Verapamil; D011493:Protein Kinase C; C018021:cobaltous chloride; D019311:Staurosporine; D009543:Nifedipine; D013755:Tetradecanoylphorbol Acetate