title: The role of adenosine in hypercarbic hyperemia: in vivo and in vitro studies in adenosine 2(A) receptor knockout and wild-type mice.
abstract: OBJECTIVE
  The authors tested the hypothesis that adenosine, acting through the A(2A) receptor, is not involved in hypercarbic hyperemia by assessing the effects of increased PaCO(2) on cerebral blood flow (CBF) in vivo in wild-type and A(2A) receptor knockout mice. In addition, they evaluated the effect of abluminal pH changes in vitro on the diameter of isolated perfused penetrating arterioles harvested from wild-type and A(2A) receptor knockout mice.
  
  
  METHODS
  The authors evaluated in a blinded fashion the CBF response during transient (60-second) hypercapnic (7% CO(2)) hypercarbia in anesthetized, ventilated C57Bl/6 wild-type and adenosine A(2A) receptor knockout mice. They also evaluated the hypercarbic response in the absence and presence of the nonselective and selective adenosine antagonists.
  
  
  RESULTS
  Cerebral blood flow was measured using laser Doppler flowmetry. There were no differences between the CBF responses to hypercarbia in the wild-type and the knockout mice. Moreover, the hypercarbic hyperemia response was not affected by the adenosine receptor antagonists. The authors also tested the response to alteration in abluminal pH in isolated perfused, pressurized, penetrating arterioles (average diameter 63.3 +/- 3.6 microm) harvested from wild-type (6 mice) and knockout (5 mice) animals. Arteriolar dilation in response to a decrease in abluminal pH, simulating the change in vivo during hypercarbia, was similar in wild-type (15.9 +/- 2.6%) and A(2A) receptor knockout (17.7 +/- 1.3%) mice. With abluminal application of CGS 21680 (10(-6) M), an A(2A) receptor agonist, wild-type arterioles dilated in an expected manner (9.8 +/- 0.7%), whereas A(2A) receptor knockout vessels had minimal response.
  
  
  CONCLUSIONS
  The results of the in vivo and in vitro studies in wild-type and A(2A) receptor knockout mice support the authors' hypothesis that hypercarbic vasodilation does not involve an adenosine A(2A) receptor-related mechanism.
authors.affiliation: Department of Neurosurgery, Mount Sinai Medical School, New York, New York, USA.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Miekisiak
authors.forename: Kristen
authors.initials: K
authors.lastname: Yoo
authors.forename: Adam L
authors.initials: AL
authors.lastname: Sandler
authors.forename: Tobias B
authors.initials: TB
authors.lastname: Kulik
authors.forename: Jiang-Fan
authors.initials: JF
authors.lastname: Chen
authors.forename: H Richard
authors.initials: HR
authors.lastname: Winn
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D006940:Hyperemia / Q000503:physiopathology*; D066298:In Vitro Techniques; D017078:Laser-Doppler Flowmetry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010313:Partial Pressure; D010627:Phenethylamines / Q000494:pharmacology; D043705:Receptor, Adenosine A2A / Q000502:physiology*
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D002245:Carbon Dioxide; D000241:Adenosine