Differential effect of cyclooxygenase inhibitors on absorptive hyperemia.
To test whether the hydrolytic products of digestion could stimulate vasoactive prostaglandin synthesis in the intestine, the muscularis and mucosa of the rat jejunum were suffused with a bicarbonate-buffered Ringer vehicle containing cyclooxygenase inhibitors (meclofenamate or indomethacin; 3 X 10(-5) M). To evoke blood flow changes, either glucose (56 mM), oleic acid (20 or 40 mM), or sodium arachidonate was added to the mucosal vehicle. Bile salt (taurocholic acid, 10 mM) was added to emulsify oleic acid. Blood flow was calculated (BFc) in submucosal arterioles by use of video microscopy. Neither bile salt nor cyclooxygenase inhibitors altered resting BFc. Neither oleic acid concentration nor solution osmolality altered the magnitude of absorptive hyperemia. After 10 min of glucose, BFc increased 36 +/- 6% with vehicle (n = 16) and 39 +/- 8% with meclofenamate (n = 10). After 10 min of oleic acid, BFc increased 21 +/- 5% with vehicle (n = 17) and 34 +/- 6% with inhibitors (n = 17). In animals exposed twice to the same concentration of oleic acid, the paired difference between the vehicle and inhibitors (19 +/- 7%; n = 9) was significant. Arachidonate alone produced no dose-related (0.06-1.9 mM) effect on BFc (n = 41), but arachidonate (0.3 mM) combined with cyclooxygenase inhibitors (6 X 10(-5) M) produced a significant BFc increase of 35 +/- 7% (n = 6). These observations suggest that the absorption of oleic acid, but not glucose, stimulates the synthesis of a vasoactive metabolite of arachidonate. The mechanism for the differential effect of cyclooxygenase inhibitors is unknown but could involve nonprostaglandin metabolites of arachidonate, such as lipoxygenase or cytochrome P-450 products.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D004063:Digestion; D005947:Glucose / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000098:blood supply / Q000187:drug effects; D007583:Jejunum / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D009829:Oleic Acids; D016718:Arachidonic Acid; D019301:Oleic Acid; D008469:Meclofenamic Acid; D005947:Glucose; D007213:Indomethacin