G-proteins in essential hypertension: a study of human platelet plasma membranes

Abstract

Aim of study: Guanine nucleotide regulatory (C) proteins act as key signal transducers for many hormones, growth factors and neurotransmitters, and have been shown to have an important influence on platelet function. As abnormal G-protein levels and activity have been reported in platelets from human non-insulin-dependent diabetics (NIDDM) we studied G-protein function in essential hypertension, a condition which is also associated with insulin resistance and in which abnormal platelet function has been reported. Methods: G-protein function was deduced from studies of adenylyl cyclase activity in platelet membrane preparations from 14 untreated essential hypertensives and 14 controls matched as far as possible for age and sex. Levels of G-protein subunits (G_sα, G_iα2 and p-subunits) were assessed by immunoblotting, using platelets from 15 subjects with untreated essential hypertension and 15 controls. Results: No changes in levels of G-proteins [G_sα, G_iα2 and P-subunits) were seen. However, in contrast to the observations in NIDDM, the studies of adenylyl cyclase function identified greater prostaglandin E-|-stimulated activity in hypertensive platelet membranes than in controls (88.8 versus 72% stimulation, P=0.018). This may have a physiological basis in protecting cells against a Ca₂₊ overload. Conclusion: These data are in opposition to the theory that a common defect in G-proteins can explain the association between hypertension and NIDDM.