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(Hypertension. 1997;29:422.)
© 1997 American Heart Association, Inc.

State-of-the-Art-Lecture

G-Protein Function Is Reduced in Hypertension

Ross D. Feldman; Jozef Chorazyczewski

From the Department of Medicine, University of Western Ontario, Canada.

Reprint requests to Dr Ross D. Feldman, Room 6L13B, London Health Sciences Center-University Campus, 339 Windermere Rd, PO Box 5339, London, Ontario, Canada N6A 5A5. E-mail ross.feldman{at}lhsc.on.ca

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 ß-adrenergic-mediated vasodilation paralleling a reduction in lymphocyte ß-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 ß-adrenoceptor-stimulated adenylyl cyclase activity.

Key Words: G-proteins • adenylyl cyclase • adrenoceptors

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