Effects of Doxazosin and Propranolol on A2A Adenosine Receptors in Essential Hypertension

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 40; no. 6; pp. 909 - 913
• Main Authors: Varani, Katia, Manfredini, Roberto, Iannotta, Valeria, Pancaldi, Cecilia, Cattabriga, Elena, Uluoglu, Canan, Borea, Pier Andrea, Portaluppi, Francesco
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.12.2002; Hagerstown, MD Lippincott
• Subjects: Adenosine-5'-(N-ethylcarboxamide) - pharmacology; Adult; Antihypertensive Agents - pharmacology; Antihypertensive Agents - therapeutic use; Arterial hypertension. Arterial hypotension; Binding, Competitive - drug effects; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Body Mass Index; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Cyclic AMP - analysis; Cyclic AMP - metabolism; Diastole; Doxazosin - pharmacology; Doxazosin - therapeutic use; Female; Humans; Hypertension - drug therapy; Hypertension - metabolism; Lymphocytes - metabolism; Male; Medical sciences; Middle Aged; Neutrophils - metabolism; Propranolol - pharmacology; Propranolol - therapeutic use; Radioligand Assay; Receptor, Adenosine A2A; Receptors, Purinergic P1 - drug effects; Receptors, Purinergic P1 - metabolism; Reference Values; Systole; Treatment Outcome; Triazines - pharmacokinetics; Triazoles - pharmacokinetics; Doxazosin; Purine nucleoside; α1-Adrenergic receptor; Cardiovascular disease; antihypertensive agents; assays; Essential; β-Adrenergic receptor; Body mass index; Alpha blocking agent; hypertension, essential; Antagonist; Propranolol; Human; Hypertension; Adenosine; receptors, adenosine; adrenergic receptor blockers; Chemotherapy; Hyperoxides; Treatment; Antihypertensive agent; Neutrophil; Adenosine receptor; Beta blocking agent
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.0000039505.79741.15

ABSTRACT—A2A adenosine receptors inhibit neutrophil adhesion and superoxide anion generation. The aim of the present study was to evaluate the effect of antihypertensive treatment with doxazosin or propranolol on the binding and functional parameters of A2A adenosine receptors of lymphocytes and neutrophils in essential hypertensive patients. Two groups of previously untreated, essential hypertensive patients were studied. The mean affinity (Kd) and density (Bmax) of adenosine receptors, by the A2A selective radioligand [H]-ZM-241385 binding assays, and EC50, by cAMP assays, were obtained first on no medication and a second time after treatment for up to 13 weeks with doxazosin (13 patients) or propranolol (8 patients). A third group of 15 healthy normotensive volunteers matched by age, sex, and body mass index was used as a control. Binding and functional parameters of the A2A adenosine receptors were significantly higher in the 2 hypertensive groups than in controls (P always <0.0001), both in lymphocyte and neutrophil membranes. After treatment with propranolol, the binding parameters did not change significantly, whereas after treatment with doxazosin, Kd, Bmax, and EC50 values returned to control levels. In never-treated essential hypertensive patients, lower affinity, higher density, and impaired function of A2A adenosine receptors are present. The binding and functional parameters of A2A adenosine receptors appear to be normalized after treatment with doxazosin but not with propranolol.