Cerebral blood flow response in adenosine 2a receptor knockout mice during transient hypoxic hypoxia.
We evaluated cerebral blood flow by laser Doppler during 30 secs of hypoxia (0.10 FiO(2)) in anesthetized, ventilated adenosine 2a receptor knockout (A2aR KO) and wild-type (WT) mice to test the hypothesis that cerebral hypoxic hyperemia in KO mice would be attenuated. We also studied the effects of selective and nonselective A2aR antagonists. During 30 secs of hypoxia, P(a)O(2) decreased significantly (P<0.05) and to a similar degree in both types of mice, whereas P(a)CO(2) remained relatively stable. However, mean arterial blood pressure (MABP) decreased to a greater extent (P<0.05) during hypoxia in KO mice (58.6+/-1.5 mm Hg) than in WT animals (76.1+/-3.2 mm Hg). Consequently, in a separate group of mice, we stabilized and matched MABP during hypoxia. Hypoxic hyperemia was attenuated by 38% (P<0.05) in KO animals whose MABP was uncontrolled, and by 81% (P<0.05) in KO animals whose MABP changes were matched to the MABP in the hypoxic WT mice. In animals treated with adenosine antagonists, hypoxic hyperemia was decreased by 44% to 48% (P<0.05) in WT mice, but was without effect in KO mice. We conclude that adenosine via A2aR is responsible for a significant proportion of the hyperemia during hypoxia.
Department of Neurosurgery, Mount Sinai Medical School, New York, New York 10029, USA.
Greg
G
Miekisiak
Tobias
T
Kulik
Yoshikazu
Y
Kusano
David
D
Kung
Jiang-Fan
JF
Chen
H Richard
HR
Winn
D058669:Adrenergic alpha-2 Receptor Antagonists; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D002316:Cardiotonic Agents / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006940:Hyperemia / Q000503:physiopathology; D002534:Hypoxia, Brain / Q000503:physiopathology*; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics* / Q000502:physiology*; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
C547769:Adra2a protein, mouse; D058669:Adrenergic alpha-2 Receptor Antagonists; D002316:Cardiotonic Agents; D018341:Receptors, Adrenergic, alpha-2; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; D000628:Aminophylline