Mechanisms of the biphasic effects of peroxides on the retinal vasculature of newborn and adult pigs.
We tested whether the ontogenic differences in the constrictor effects of peroxides on the retinal vasculature were modulated by dilator cyclo-oxygenase products. Retinal arteriole (100-200 microns) vasomotor response to H2O2, t-butyl hydroperoxide, and cumene hydroperoxide were studied in isolated eyecup preparations using video camera monitoring of vessel diameter. A time- and dose-dependent biphasic retinal vasomotor response to all peroxides was observed on tissues of newborn and adult pigs. A rapid vasoconstriction (first 2 min) was followed by a relaxation which was greater in the adult than in the newborn tissues. The constrictor as well as the dilator response to peroxides and the observed increase in prostanoids were blocked by the cyclo-oxygenase inhibitor indomethacin. The peroxide-induced relaxation was inhibited or markedly attenuated by the prostaglandin I2 synthase blockers, trans-2-phenyl cyclopropylamine and minoxidil on tissues of newborn and adult animals. These agents also prevented the increase of the prostaglandin I2 receptor-coupled second messenger, cyclic 3',5'-adenosine monophosphate. Our data indicate that prostaglandin I2 plays a major role in counteracting the initial constrictor effects of peroxides in the retinal vasculature, and that the reversal of this constriction is greater in the adult than the newborn. These findings suggest that reduced reversal of vasoconstriction by the dilator prostaglandin I2 during an oxidative stress in the newborn may facilitate vasoconstriction by the dilator prostaglandin I2 during an oxidative stress in the newborn may facilitate neovascularization in retinopathy of prematurity.
Abran
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D
Centre de Recherche de l'Hôpital Sainte-Justine, Department of Pediatrics, Montréal, Québec, Canada.
Hardy
P
P
Varma
D R
DR
Chemtob
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S
D000818:Animals; D000831:Animals, Newborn; D001555:Benzene Derivatives / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000494:pharmacology; D010545:Peroxides / Q000494:pharmacology*; D012171:Retinal Vessels / Q000187:drug effects*; D013552:Swine; D013929:Thromboxane B2 / Q000378:metabolism; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D001555:Benzene Derivatives; D016861:Cyclooxygenase Inhibitors; D010545:Peroxides; D013929:Thromboxane B2; D006861:Hydrogen Peroxide; D000242:Cyclic AMP; C007164:cumene hydroperoxide