ENDOTHELIAL AND NONENDOTHELIAL CYCLOOXYGENASE MEDIATE RABBIT PIAL ARTERIOLE DILATION BY BRADYKININ

Citation
Jr. Copeland et al., ENDOTHELIAL AND NONENDOTHELIAL CYCLOOXYGENASE MEDIATE RABBIT PIAL ARTERIOLE DILATION BY BRADYKININ, American journal of physiology. Heart and circulatory physiology, 37(1), 1995, pp. 458-466
Citations number
67
Categorie Soggetti
Physiology
ISSN journal
03636135
Volume
37
Issue
1
Year of publication
1995
Pages
458 - 466
Database
ISI
SICI code
0363-6135(1995)37:1<458:EANCMR>2.0.ZU;2-2
Abstract
Aspirin (acetylsalicylic acid, ASA) was administered to rabbits in an attempt to inhibit selectively endothelial cyclooxygenase activity and therefore to determine its role in bradykinin-induced radical-mediate d dilation of cerebral arterioles. With the use of the cranial window technique in anesthetized rabbits, pial arteriolar diameters were reco rded in response to topically applied bradykinin, acetylcholine, and v entilation with 10% O-2-9% CO2 gas mixture. Prostaglandins were measur ed in isolated cerebral microvessels and cerebrospinal fluid (CSF) usi ng radioimmunoassay. Microvessel prostaglandin production was reduced significantly by 90 mg/kg iv ASA, whereas acetylcholine-stimulated inc reases of CSF prostaglandins were not similarly affected. This treatme nt reduced bradykinin-induced dilation of pial arterioles by 47%. Afte r concurrent 90 mg/kg iv ASA plus 300 mu M ASA topically applied to th e brain, stimulated increases of CSF prostaglandins were reduced by 79 %, while bradykinin-induced dilation was reduced by 78%. ASA did not r educe the dilator activity of either acetylcholine or ventilation with 10% O-2-9% CO2. Acetylcholine- but not bradykinin-induced dilation wa s reduced by N-G-nitro-L-arginine methyl ester. These results indicate intravenous ASA produced a relatively selective inhibition of cerebra l microvascular cyclooxygenase and partial inhibition of bradykinin-in duced dilation. Further inhibition of dilation occurred following ASA administered both systemically and topically to the brain. This indica tes two sources of cyclooxygenase, endothelial and nonendothelial, med iate the bradykinin-induced dilation of rabbit pial arterioles. Furthe rmore, systemic doses of ASA do not eliminate brain prostaglandin form ation.