G-protein function is reduced in hypertension.
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.
Feldman
R D
RD
Department of Medicine, University of Western Ontario, Canada. ross.feldman@lhsc.on.ca
Chorazyczewski
J
J
D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D000367:Age Factors; D005576:Colforsin / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism*; D008875:Middle Aged
D000318:Adrenergic beta-Agonists; D005576:Colforsin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases