Action of protein kinase c in endothelin-induced contractions in
rat aortic rings.
Oriji, Gibson K., and Harry R. Keiser.
Hypertension-Endocrine Branch, National Heart Lung and Blood
Institute, National Institutes of Health, Bethesda, MD 20892
APStracts 3:0034C, 1996.
Endothelin (ET) is a potent vasoconstrictor peptide that induces
characteristically long-lasting contractions. We used both intact and
endothelium-denuded rat aortic rings to investigate the role of
protein kinase C (PKC) in ET-induced contractions. ET (10-9M) and
Phorbol 12, 13-dibutyrate (PDBu), a PKC activator, produced a gradual
and sustained contraction of greater magnitude in denuded aortic
rings than in intact rings. When aortic rings were pretreated with
graded concentrations of different PKC inhibitors, inhibition of ET
-induced contractions began at 10-9M, was nearly complete at 10-3M.,
and the reduction was greater in intact than in denuded rings.
Pretreatment of aortic rings with PDBu or NG-Nitro-L-arginine Methyl
Ester, (L-NAME), an inhibitor of nitric oxide synthase, potentiated
ET-induced contractions. PKC enzyme assay showed activation of PKC in
aortic rings that were treated with either ET or PDBu, inhibition
after pretreatment with PKC inhibitors and no change with 4-alpha
-phorbol, 12,13-Didecanoate (PDD), an inactive phorbol ester. ET
significantly increased nitrate/nitrite production which was further
increased by pretreatment with PKC inhibitors. PDBu prevented ET
-induced nitrate/nitrite production and PDD had no effect. These
results strongly suggest that PKC mediates, in part, ET-induced
contractions in rat aortic rings, and that an intact endothelium is
required for maximum inhibition by PKC inhibitors because PKC
stimulated by ET inhibits nitric oxide (NO) release.
Received 20 June 1995; accepted in final form 12 January 1996.
APS Manuscript Number C358-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 January 96