title: Role of adenosine A2 receptors in regulation of cerebral blood flow during induced hypotension.
abstract: The mechanisms responsible for vascular autoregulation in the brain during changes in mean arterial blood pressure are ambiguous. Potentially, adenosine, a purine nucleoside and potent vasodilator, may be involved as earlier studies have documented an increase in brain adenosine concentrations with cerebral ischemia and hypotension. Consequently, we tested the hypothesis that adenosine is involved in vasodilatation during hypotension within the autoregulatory range (>50 mm Hg) by exposing adenosine 2a receptor (A2aR) knockout and wild type (WT) mice to short (2 to 5 mins) periods of hypotension. We found that autoregulation was significantly (P<0.05) impaired by 29% in A2a knockout mice as compared with WT animals. Furthermore, the A2R antagonist (A2a>A2b:10-85>1), ZM-241385, in a dose (1, 5, 10 mg/kg, intraperitoneally)-related manner, attenuated autoregulation in WT mice. In knockout mice treated with ZM-2413585 (5 and 10 mg/kg), autoregulation was further impaired indicating that A2b receptors also participated in cerebral vasodilatation. Treatment with dipyridamole (1.0 mg/kg) that increases extracellular concentrations of adenosine improved autoregulation in the A2aR knockout mice. We would conclude that adenosine through both A2a and A2b receptors is involved in physiologic vascular regulation during hypotension even within the autoregulatory range.
authors.affiliation: Department of Neurosurgery, Mount Sinai Medical School, New York, New York 10029, USA.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kusano
authors.forename: German
authors.initials: G
authors.lastname: Echeverry
authors.forename: Greg
authors.initials: G
authors.lastname: Miekisiak
authors.forename: Tobias B
authors.initials: TB
authors.lastname: Kulik
authors.forename: Shimon N
authors.initials: SN
authors.lastname: Aronhime
authors.forename: Jiang F
authors.initials: JF
authors.lastname: Chen
authors.forename: H Richard
authors.initials: HR
authors.lastname: Winn
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004176:Dipyridamole / Q000378:metabolism; D007022:Hypotension / Q000139:chemically induced*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010627:Phenethylamines / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000378:metabolism*; D043704:Receptor, Adenosine A2B / Q000378:metabolism*; D014227:Triazines / Q000378:metabolism; D014230:Triazoles / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology; D014665:Vasodilator Agents / Q000378:metabolism
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D000959:Antihypertensive Agents; D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D014227:Triazines; D014230:Triazoles; D014665:Vasodilator Agents; C097270:ZM 241385; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D004176:Dipyridamole; D000241:Adenosine