G-protein function is reduced in hypertension.

Abstract

A functional impairment in vasodilator tone may be important in the pathogenesis and/or maintenance of elevated peripheral vascular resistance in hypertension. Previous studies of hypertensive subjects have demonstrated impaired beta-adrenergic-mediated vasodilation paralleling a reduction in lymphocyte beta-adrenergic-stimulated adenylyl cyclase activity. We have suggested that this impairment is related to a defect in G-protein function. To determine whether this defect alters the coupling between the G-protein complex and adenylyl cyclase, we performed [3H]forskolin binding studies in lymphocytes from hypertensive subjects, older normotensive subjects, and younger normotensive control subjects. Maximal specific [3H]forskolin binding was used as an index of adenylyl cyclase binding sites. Gpp(NH)p-, NaF/AlCl3-, and isoproterenol-stimulated binding were used as indices of G-protein/adenylyl cyclase coupling. In the absence of other stimulators, maximal [3H]forskolin binding was not significantly different among groups. However, both Gpp(NH)p- and isoproterenol-stimulated [3H]forskolin binding were significantly decreased in lymphocytes from hypertensive subjects. Overall, Gpp(NH)p- and isoproterenol-stimulated [3H]forskolin binding were significantly inversely correlated with blood pressure. No differences in NaF/AlCl3-stimulated [3H]forskolin binding were detected between groups. These studies indicate that G-protein/adenylyl cyclase coupling is impaired in lymphocytes from younger hypertensive subjects and may contribute to the blood pressure-related defect in beta-adrenoceptor-stimulated adenylyl cyclase activity.