The role of prostaglandins in the endothelium-mediated vasodilatory response to hypoxia.
The effect of intraluminal hypoxia on vascular tone and the release of prostaglandins (PG) I2 and E2 were investigated in intact isolated segments of canine femoral and coronary arteries as well as in the rat tail artery. Perfusion with hypoxic Tyrode's solution (pO2: 20-40 mm Hg) evoked a marked vasodilation of the segments, precontracted with norepinephrine or serotonin. Simultaneously, a 2-3-fold increase in the release of 6-keto-PGF1 alpha (the stable hydrolysis product of PGI2) could be observed. In parallel to 6-keto-PGF1 alpha, smaller quantities of PGE2 were released. Removal of the endothelium as well as pretreatment with indomethacin abolished both, the dilatory response and the PG-release. After administration of verapamil as well as 3,4,5-trimethoxybenzoic acid 8-diethylaminooctylester (TMB-8) (which binds intracellular calcium) the PG-increase was abolished and hypoxic dilatation could no longer be elicited, although the vessel had still a capacity to dilate. Exogenous administration of PGI2 and PGE2 showed that in canine femoral and coronary arteries PGI2 was the most effective vasodilating prostaglandin, while in the rat tail artery PGE2 had a 10-fold higher dilating potency compared to PGI2. At very high concentrations both PGI2 and PGE2 caused vasoconstriction. Our experiments suggest that the hypoxic endothelium-dependent dilatation may be mediated by an increased PG-release. Hypoxia-induced transmembrane calcium influx into the endothelial cells seems to be the trigger reaction.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015232:Dinoprostone; D004285:Dogs; D004727:Endothelium / Q000187:drug effects / Q000502:physiology*; D011464:Epoprostenol / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*; D011458:Prostaglandins E / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D011453:Prostaglandins; D011458:Prostaglandins E; D015121:6-Ketoprostaglandin F1 alpha; D014700:Verapamil; D011464:Epoprostenol; D015232:Dinoprostone; D010100:Oxygen; D002118:Calcium; D007213:Indomethacin