Beta-adrenergic receptor alterations in hypertension--physiological and molecular correlates.

Abstract

In hypertensive animals, there is physiological and biochemical evidence that beta-adrenergic responsiveness is diminished. In contrast, in man the physiological evidence of reduced beta-adrenergic responsiveness is not completely convincing and few biochemical studies have been reported. The lymphocyte has been widely used as a model for the human beta-adrenergic receptor complex. In studies comparing young normotensive and mild hypertensive subjects we demonstrated a reduction in beta-adrenergic mediated adenylate cyclase activity in lymphocytes from hypertensive subjects. A parallel reduction in beta-adrenergic receptor affinity for agonists was also seen. These changes are consistent with a functional uncoupling of the receptor from the adenylate cyclase complex. To determine the role of dietary sodium intake on beta-adrenergic receptor properties in hypertension we studied lymphocytes from hypertensive and normotensive subjects fed either a low (10 mequiv.) or high (400 mequiv.) NaCl diet. We demonstrated that a low NaCl diet corrected the defect in lymphocyte beta-adrenergic responsiveness in hypertension. These studies emphasize the utility of biochemical approaches to the study of alterations in beta-adrenergic responsiveness in human hypertension and suggest an important role of dietary sodium in the reduction in beta-adrenergic responsiveness in the hypertensive state.