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(Hypertension. 1996;28:83-90.)
© 1996 American Heart Association, Inc.

Articles

Aberrant Adenylyl Cyclase/cAMP Signal Transduction and G Protein Levels in Platelets From Hypertensive Patients Improve With Antihypertensive Drug Therapy

Josee Marcil; Ernesto L. Schiffrin; Madhu B. Anand-Srivastava

the Department of Physiology, Faculty of Medicine, Groupe de recherche sur le systeme nerveux autonome (J.M., M.B.A.-S.), and Clinical Research Institute of Montreal (E.L.S.), University of Montreal (Canada).

Correspondence to Dr Madhu B. Anand-Srivastava, Department of Physiology, Faculty of Medicine, University of Montreal CP 6128, Succursale A, Montreal, Quebec, Canada H3C 3J7.

We have previously demonstrated a decreased expression of G_i2 protein in platelets from spontaneously hypertensive rats that was associated with an altered responsiveness of adenylyl cyclase to hormone stimulation and inhibition. In the present studies, we have used platelets from hypertensive patients and examined the hormonal regulation of adenylyl cyclase as well as the levels of G proteins and their modulation by antihypertensive drug therapy. We performed these studies in platelets from four groups of subjects: normotensive subjects (group 1), untreated mildly essential hypertensive patients (group 2), and treated moderately to severely hypertensive patients whose blood pressure was uncontrolled (group 3) or controlled with drug treatment (group 4). GTPS, 5'-(N-ethylcarboxamido)adenosine (NECA), and prostaglandin E₁ stimulated adenylyl cyclase activity to a greater extent in hypertensive patients (group 2). This effect was partially corrected (by approximately 50% to 80%) in the patients under antihypertensive drug therapy (groups 3 and 4). In addition, inhibition of adenylyl cyclase mediated by a ring-deleted analogue of atrial natriuretic factor (C-ANF_4-23) observed in control normotensive subjects was blunted in hypertensive patients (group 2) and was not corrected in treated patients. G_s levels determined by immunoblotting were in the same range for the four groups, whereas G_i2 and G_i3 levels were decreased by 70% and 60%, respectively, in hypertensive patients (group 2) compared with normotensive subjects. Antihypertensive drug therapy (groups 3 and 4) partially restored G_i2 levels toward normal (group 1) by about 60% and 70%, respectively; however, the reduced G_i3 levels in group 2 hypertensive patients were not improved in group 3 but were raised toward normal levels in group 4 by about 55%. These results suggest that the altered responsiveness of platelet adenylyl cyclase to hormones in hypertension and the normalization of the response with antihypertensive drug therapy could partly be due to the ability of the latter to modulate G_i protein expression. These effects on platelet function may underlie the beneficial effects of antihypertensive agents on some of the complications of hypertension.

Key Words: adenyl cyclase • G proteins • platelets • hypertension, essential • antihypertensive therapy

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