title: Severe hypoxia inhibits prostaglandin I(2) biosynthesis and vasodilatory responses induced by ionophore A23187 in the isolated rabbit ear.
abstract: The present study was designed to test the hypothesis that lack of oxygen in severely hypoxic tissue may inhibit arachidonic acid oxygenation and thereby result in an inhibition of eicosanoid synthesis. Hypoxia was induced in the isolated rabbit ear, and arachidonate metabolism and peripheral resistance of the preparation were monitored simultaneously. Severe hypoxia completely inhibited the biosynthesis of prostaglandin I(2) induced by ionophore A23187 and converted the vasodilatory response observed under normoxia into vasoconstriction. The cyclooxygenase 1 inhibitor SC560 (1 micromol/l) effectively inhibited the normoxic prostaglandin I(2) biosynthesis, while the cyclooxygenase 2 inhibitor DFU (1 micromol/l) did not. Neither SC560 nor DFU affected normoxic vasodilatory responses, indicating no involvement of prostanoids. The nitric oxide (synthase inhibitor Nomega-nitro-L-arginine methyl ester (100 micromol/l) converted the vasodilation into vasoconstriction, similar to what was observed under hypoxia, suggesting that the hypoxia-mediated conversion might occur due to the inhibition of nitric oxide.
authors.affiliation: Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovakia. ivo.juranek@seznam.cz
authors.forename: Ivo
authors.initials: I
authors.lastname: Juránek
authors.forename: Viktor
authors.initials: V
authors.lastname: Bauer
authors.forename: Josef
authors.initials: J
authors.lastname: Donnerer
authors.forename: Fred
authors.initials: F
authors.lastname: Lembeck
authors.forename: Bernhard A
authors.initials: BA
authors.lastname: Peskar
mesh_terms: D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D004423:Ear; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D000860:Hypoxia / Q000378:metabolism*; D007476:Ionophores / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects
chemical_list: D007476:Ionophores; D000001:Calcimycin; D011464:Epoprostenol