Prostaglandin action, release and inactivation by rat isolated perfused mesenteric blood vessels.
1 The following experiments were undertaken to confirm that prostaglandin is necessary for noradrenaline to exert its full vasoconstrictor effect in rat mesenteric blood vessels. Prostaglandin release and inactivation were also studied. 2 The cyclo-oxygenase inhibitor, 5, 8, 11, 14-eicosatetraynoic acid caused a significant depression of the concentration-effect curve to noradrenaline. As with indomethacin, responses were restored to control levels by prostaglandin E2 (PGE2) but PGE2 did not restore responses to noradrenaline depressed by papaverine. 3 PGE2-like activity was released from tissues at rest, equivalent to 50 +/- 20 pg PGE2/min. The substance was probably a stable prostaglandin since activity remained on acidifying and extracting into chloroform. The increase in release stimulated by noradrenaline was reduced below resting values by indomethacin. 4 There was a net loss of 7 +/- 1 and 1 +/- 0.2 ng PGE2/min from tissues perfused with 40 and 4 ng/min PGE2 respectively. No uptake occurred at lower PGE2 perfusion rates. 5 When indomethacin was used to depress responses to noradrenaline 15(S)-15-methyl PGE2 methyl ester was 12 times more potent than PGE2 in restoring responses to control values. The cyclic endoperoxide analogue U-46619 caused only partial restoration of indomethacin-depressed responses to noradrenaline but increased perfusion pressure at 2 ng/ml and above. 6 The results confirm that endogenous prostaglandin release, possible of PGE2, is obligatory to the full vasoconstrictor effect of noradrenaline. Noradrenaline increases the amount of prostaglandin released which may be taken up and inactivated by 15-hydroxy prostaglandin dehydrogenase or beta-oxidase. U-46619 may mimic both PGE2 and thromboxane A2.
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008643:Mesentery / Q000098:blood supply; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D014662:Vasoconstrictor Agents
D011450:Prostaglandin Endoperoxides, Synthetic; D011453:Prostaglandins; D011458:Prostaglandins E; D014662:Vasoconstrictor Agents; D015117:5,8,11,14-Eicosatetraynoic Acid; D007213:Indomethacin