Decreased sensitivity of adenylate cyclase to sodium ions in lymphocytes of patients with arterial hypertension

Abstract

Patients with arterial hypertension showed decreased sensitivity of isoproterenol-stimulated adenylate cyclase of mononuclear lymphocytes toward sodium ions compared with normotensive donors. Ouabain, an inhibitor of Na, K-ATPase, increased the half-maximal inhibition of adenylate cyclase activity by sodium ions in the cells of healthy subjects and did not change enzyme sensitivity to sodium in the lymphocytes of hypertensive patients.Key Words: sodium; adenylate cyclase; lymphocytes; arterial hypertension; ouabain Changes in the production of different neurotransmitters and hormonal factors, as well as alterations in the cellular mechanisms of hormonal signal transmission via membrane receptors and in the transport of calcium and monovalent cations are typical features of hypertension [4,14]. Progression of the disease is attended by a decrease in adenylate cyclase (AC) affinity to catecholamines in peripheral blood lymphocytes [8] and a rise in the intracellular concentration of sodium ions in erythrocytes and lymphocytes [3,11]. Interaction of a-and [3-adrenergic receptors with ligands is modulated allosterically by monovalent cations (Na+>Li+>K+), while changes in the receptor affinity to catecholamines correlate with the changes in the intraeellular sodium concentration [10,12,13]. Sodium exerts an inhi'bitory effect on AC activity [7]. Data on the phosphorylation of the ct-subunit of Na,K-ATPase by cAMP-dependent protein kinase A and protein kinase C suggest the existence of multiple bonds between the Na,K-ATPase system of active transport of monovalent cations and the cAMP system [6]. Our previous studies demonstrated that the Na,K- ATPase inhibitor ouabain modulates AC activity in the lymphocytes of healthy donors [1] and alters cyclase sensitivity to sodium ions [2]. The purpose of the present study was to investigate the inhibitory effect of sodium on AC activity in the lymphocytes-of patients with arterial hypertension (AH) compared with the cells of normotensive donors. MATERIALS AND METHODSStudies were performed on freshly isolated mononuclear peripheral blood lymphocytes taken from healthy donors and patients with pronounced AH. Cells of 11 normotensive males aged 47+2 years and of 10 males aged 49+3 years with stage IIA of AH according to the classification of Myasnikov (mean arterial pressure 130+3.3 mm Hg) were used in the study. The patients received no medication for 2 weeks prior to the study. For the isolation of lymphocytes blood was taken at 09:00 h from the ulnar vein (from a fasting patient) lying down. The fraction of mononuclear lymphocytes was isolated on a Ficoll-Verographin gradient according to a modified technique [2,5].Basal and isoproterenol-stimulated (100 ~tM) AC activity was determined in lymphocyte homogenates by the method of Salomon [15]