Role of adenosine A(2B) receptors in vasodilation of rat pial artery and cerebral blood flow autoregulation.
This study was aimed to investigate the underlying mechanism of vasodilation induced by the activation of A(2B) adenosine receptors in relation to cerebral blood flow (CBF) autoregulation. Changes in pial arterial diameters were observed directly through a closed cranial window. N(omega)-nitro-L-arginine methyl ester (L-NAME, nitric oxide synthase inhibitor) significantly suppressed the concentration-dependent vasodilations induced by adenosine and 5'-N-ethylcarboxamido-adenosine (NECA) but not the vasodilation by CGS-21680 (A(2A)-receptor agonist). Moreover, NECA-induced vasodilation was suppressed by alloxazine (1 micromol/l) but not by ZM-241385 (1 micromol/l, A(2A) antagonist), which suggests mediation by A(2B)- receptor activation. Otherwise, the level of nitrite/nitrate was concentration dependently increased in the artificial cerebrospinal fluid (CSF) when adenosine and NECA were suffused over the cortical surface. L-NAME and alloxazine, but not ZM-241385, largely inhibited their releases. The lower limit of CBF autoregulation was little affected following pretreatment with L-NAME or alloxazine. Thus it is suggested that adenosine-induced vasodilation via activation of A(2B)-adenosine receptors of the rat pial artery is coupled to the production of nitric oxide, which contributes little to CBF autoregulation.
Shin
H K
HK
Department of Pharmacology, College of Medicine, Pusan National University, Pusan 602-739, Korea.
Shin
Y W
YW
Hong
K W
KW
D000818:Animals; D001158:Arteries / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005415:Flavins / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010841:Pia Mater / Q000098:blood supply*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043704:Receptor, Adenosine A2B; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D005415:Flavins; D009566:Nitrates; D009573:Nitrites; D043704:Receptor, Adenosine A2B; D018047:Receptors, Purinergic P1; D013873:Thionucleotides; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; C083763:8-bromoguanosino-3',5'-cyclic monophosphorothioate; C016957:adenosine-3',5'-cyclic phosphorothioate; C008173:isoalloxazine; D000242:Cyclic AMP; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester