Regulation of the lymphocyte adenylate cyclase system by prostaglandin E2 infusions in resistant hypertensive subjects.

Abstract

The effects of prostaglandin E2 (PGE2) infusions on the beta 2-adrenoceptor-dependent adenylate cyclase (beta 2ARAC) system of lymphocytes were studied in 26 patients with resistant hypertension (RH). The density of beta 2-adrenoceptors and their affinity for l-isoproterenol were measured with 125ICYP, and adenylate cyclase activity was determined with alpha 32P-ATP in mononuclear lymphocytes of RH patients before and at 1, 7, and 14 days after the last PGE2 infusion. Plasma epinephrine and norepinephrine concentrations were analyzed using high-performance liquid chromatography. The patients were divided into two groups: 19 receiving clonidine (group I) and seven receiving four-drug antihypertensive therapy (group II) before and after PGE2 infusions. Resistance to antihypertensive drugs in patients of both groups was overcome by PGE2 infusions, and was correlated with a decrease in lymphocyte beta 2-adrenoceptor density, an increase in beta 2-receptor affinity for l-isoproterenol, and an increase in adenylate cyclase activation. The absence of a PGE2 effect was associated with an acute increase in plasma epinephrine content and a decrease in the sensitivity of the lymphocyte beta 2ARAC system.