An inhibitory effect of arachidonic acid on subsequent responses of canine cerebral arteries to serotonin and other agonists.
Arachidonic acid (AA) at 10(-4)M and 10(-3)M produced a phasic contraction in isolated canine basilar arteries that peaked rapidly and then slowly declined. This contraction was evidently due to the conversion of AA to prostanoids because it was blocked by cyclooxygenase inhibitors and because 11, 14, 17 eicosatrienoic acid (10(-3)M), which is not a cyclooxygenase substrate, failed to produce a contraction. When the artery was exposed to 10(-3)M AA for 20 min and washed, subsequent contractile responses to 10(-6)M serotonin (5-HT) were only 10% of control. Contractions produced by prostaglandin E2 (10(-5)M), uridine triphosphate (10(-4)M) and potassium (5.5 X 10(-4)M) were inhibited to a lesser degree than 5-HT, the response to potassium being the least affected (66% of control). This damaging effect of 10(-3)M AA did not occur if the artery was washed at peak contraction nor with 10(-4)M AA. Autooxidation products were evidently not responsible for the damage because prior oxygenation (90 min) of 10(-4)M AA had no such effect. Pretreatment with superoxide dismutase or ascorbate did not prevent the inhibition, suggesting that free radical reactions were not involved. Pretreatment with indomethacin (3 X 10(-4)M) or meclofenamate (10(-4)M) also failed to prevent the inhibitory phenomenon. Saponin, a detergent, produced similar inhibitory effects but 11, 14, 17 eicosatrienoic acid or oleate (10(-3)M) did not. The arteries partially recovered from the inhibition with time. In conclusion, AA produced contraction in basilar arteries by inducing prostaglandin synthesis but can produce secondarily by an unidentified mechanism an inhibition of the contractile responses evoked by various agonists that is both time and concentration dependent.
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects*; D015232:Dinoprostone; D004285:Dogs; D005609:Free Radicals; D009119:Muscle Contraction / Q000187:drug effects; D009829:Oleic Acids / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D012503:Saponins / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D014544:Uridine Triphosphate / Q000494:pharmacology
D001095:Arachidonic Acids; D005609:Free Radicals; D009829:Oleic Acids; D011458:Prostaglandins E; D012503:Saponins; D012701:Serotonin; D013482:Superoxide Dismutase; D015232:Dinoprostone; D014544:Uridine Triphosphate