Hypertension, Vol 23, 722-728, Copyright © 1994 by American Heart Association
A Calderone, L Oster, P Moreau, JL Rouleau, DJ Stewart and J de Champlain
This study examined the contribution of phosphatidylinositol metabolism and
the efficacy of protein kinase C-mediated desensitization in the
exaggerated alpha 1b-adrenergic receptor-mediated inositol phosphate
response in the aorta of the deoxycorticosterone acetate (DOCA)-salt rat
model of hypertension. The basal accumulation of inositol phosphates and
the basal incorporation of [3H]myo-inositol in the phosphatidylinositol
lipid pool were significantly higher in the aorta of these hypertensive
rats. A positive correlation (r = .88, P < .01) was demonstrated between
basal inositol phosphate levels and the [3H]myo-inositol-labeled
phosphatidylinositol lipid pool. In hypertensive rats, alpha 1b-adrenergic
receptor-mediated inositol phosphate production in response to
phenylephrine was significantly higher compared with normotensive rats.
Despite the normalization of phenylephrine-mediated inositol phosphate
production to the [3H]myo- inositol-labeled phosphatidylinositol lipid
pool, the alpha 1b- adrenergic response remained significantly higher in
the hypertensive rats. Phorbol ester activation of protein kinase C
attenuated to a lesser extent phenylephrine-mediated inositol phosphate
production (40%) in the aorta of hypertensive rats compared with the 80%
attenuation observed in the aorta of normotensive rats. This
desensitization was inhibited in both groups by the protein kinase C
inhibitor staurosporine. The blunted desensitization of the alpha 1b-
adrenergic receptor by protein kinase C activation was not associated with
a decrease in protein kinase C activity in the hypertensive rats, because
aortic strips from these animals were more responsive to phorbol ester
activation than aortic strips from normotensive animals.(ABSTRACT TRUNCATED
AT 250 WORDS)
ARTICLES
Altered protein kinase C regulation of phosphoinositide-coupled receptors in deoxycorticosterone acetate-salt hypertensive rats
Faculty of Medicine, Department of Physiology, Universite de Montreal, Quebec, Canada.
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