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Hypertension. 1994;23:722-728

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Hypertension, Vol 23, 722-728, Copyright © 1994 by American Heart Association


ARTICLES

Altered protein kinase C regulation of phosphoinositide-coupled receptors in deoxycorticosterone acetate-salt hypertensive rats

A Calderone, L Oster, P Moreau, JL Rouleau, DJ Stewart and J de Champlain
Faculty of Medicine, Department of Physiology, Universite de Montreal, Quebec, Canada.

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)


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