AJP - Cell Physiology, Vol 259, Issue 3 C421-C426, Copyright © 1990 by American Physiological Society
Role of protein kinase C in renal vasoconstriction caused by angiotensin II
H. Scholz and A. Kurtz
Physiologisches Institut, Universitat Zurich, Switzerland.
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.
