Adenosine receptors mediate glutamate-evoked arteriolar dilation in the rat cerebral cortex.
We tested the hypothesis that adenosine (Ado) mediates glutamate-induced vasodilation in the cerebral cortex by monitoring pial arteriole diameter in chloralose-anesthetized rats equipped with closed cranial windows. Topical application of 100 microM glutamate and 100 microM N-methyl-d-aspartate (NMDA) dilated pial arterioles (baseline diameter 25 +/- 2 microm) by 17 +/- 1% and 18 +/- 4%, respectively. Coapplication of the nonselective Ado receptor antagonist theophylline (Theo; 10 microM) significantly reduced glutamate- and NMDA-induced vasodilation to 4 +/- 2% (P < 0.01) and 6 +/- 2% (P < 0.05), whereas the Ado A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (0.1 microM) had no effect. Moreover, application of the Ado A(2A) receptor-selective antagonist 4-(2-[7-amino-2-(2-furyl)(1,2,4)triazolo(2,3-a)(1,3,5)triazin-5-ylamino]ethyl)phenol (ZM-241385), either by superfusion (0.1 microM, 1 microM) or intravenously (1 mg/kg), significantly inhibited the pial arteriole dilation response to glutamate. Neither Theo nor ZM-241385 affected vascular reactivity to mild hypercapnia induced by 5% CO(2) inhalation. These results suggest that Ado contributes to the dilation of rat cerebral arterioles induced by exogenous glutamate, and that the Ado A(2A) receptor subtype may be involved in this dilation response.
Iliff
Jeffrey J
JJ
Department of Neurological Surgery, University of Washington School of Medicine, Harborview Medical Center, 325 Ninth Avenue, Seattle, WA 98104, USA.
D'Ambrosio
Raimondo
R
Ngai
Al C
AC
Winn
H Richard
HR
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D018690:Excitatory Amino Acid Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; D018698:Glutamic Acid; D016202:N-Methylaspartate