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
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.