title: Effects of doxazosin and propranolol on A2A adenosine receptors in essential hypertension.
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 (K(d)) and density (B(max)) of adenosine receptors, by the A2A selective radioligand [3H]-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, K(d), B(max), 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.
authors.affiliation: Pharmacology Unit, Department of Clinical and Experimental Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Varani
authors.forename: Roberto
authors.initials: R
authors.lastname: Manfredini
authors.forename: Valeria
authors.initials: V
authors.lastname: Iannotta
authors.forename: Cecilia
authors.initials: C
authors.lastname: Pancaldi
authors.forename: Elena
authors.initials: E
authors.lastname: Cattabriga
authors.forename: Canan
authors.initials: C
authors.lastname: Uluoglu
authors.forename: Pier Andrea
authors.initials: PA
authors.lastname: Borea
authors.forename: Francesco
authors.initials: F
authors.lastname: Portaluppi
mesh_terms: D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001667:Binding, Competitive / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism; D003971:Diastole; D017292:Doxazosin / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology* / Q000627:therapeutic use; D011869:Radioligand Assay; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000187:drug effects* / Q000378:metabolism; D012016:Reference Values; D013599:Systole; D016896:Treatment Outcome; D014227:Triazines / Q000493:pharmacokinetics; D014230:Triazoles / Q000493:pharmacokinetics
chemical_list: D000959:Antihypertensive Agents; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; D019830:Adenosine-5'-(N-ethylcarboxamide); D011433:Propranolol; D000242:Cyclic AMP; D017292:Doxazosin