The role of prostaglandins in the endothelium-mediated vasodilatory response to hypoxia |
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Authors: | R Busse U Förstermann H Matsuda U Pohl |
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Institution: | (1) Lehrstuhl f. Angew Physiologie, Universität Freiburg i. Br., Hermann-Herder-Strasse 7, D-7800 Freiburg i. Br., Federal Republic of Germany;(2) Pharmakologisches Institut, Universität Freiburg i. Br., Hermann-Herder-Strasse 5, D-7800 Freiburg i. Br., Federal Republic of Germany |
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Abstract: | 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 (the stable hydrolysis product of PGI2) could be observed. In parallel to 6-keto-PGF1, 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-diethyl-aminooctylester (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.Supported by the Deutsche Forschungsgemeinschaft (Bu 436/2-1) |
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Keywords: | Arterial smooth muscle Endothelial cells Hypoxia Prostaglandins Endothelium-dependent dilatation Radioimmunoassay Verapamil |
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