Regulation of prostanoid vasomotor effects and receptors in choroidal vessels of newborn pigs.
This study was conducted to determine if high perinatal prostaglandin (PG) and thromboxane (TxA2) levels modified their choroidal vasomotor effects and receptor levels. Both nonperfused (eyecup preparations) and perfused choroidal vessels from saline- or ibuprofen-treated 1-day-old pigs and tissues from adult pigs were used; all prostanoids produced similar vasomotor effects on both preparations. Choroidal PGF2alpha, TxA2, PGI2, and PGD2 levels were higher in the newborn than in adult pigs; injections of ibuprofen (40 mg/kg every 4 h for 48 h) into newborn pigs significantly decreased choroidal levels of all these prostanoids. PGF2alpha and the TxA2 mimetic U-46619 caused less choroidal vasoconstriction and production of inositol 1,4,5-trisphosphate (IP3) in the newborn than in adult pigs. Ibuprofen treatment increased choroidal PGF2alpha vasoconstrictor effects, IP3 production, and receptors, but did not modify response to U-46619. Carbaprostacyclin (PGI2 analog) caused a greater choroidal vasodilatation and adenosine adenosine 3',5'-cyclic monophosphate (cAMP) production in the newborn than in adult pigs; these effects were not modified by ibuprofen. PGD2 did not increase cAMP but caused greater dilatation and nitrite [oxidation product of nitric oxide (NO)] production in the choroid of newborn than of adult pigs, which were decreased to adult levels by ibuprofen and the NO synthase inhibitor N(omega)-nitro-L-arginine. These data suggest that high perinatal PG levels downregulate PGF2alpha receptors and vascular effects but do not modify choroidal responses to TxA2 and PGI2; NO seems to contribute to the vasodilator effects of PGD2.
Abran
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Centre de Recherche de l'Hôpital Sainte-Justine, Department of Pediatrics, Montréal, Québec, Canada.
Varma
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Chemtob
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D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002829:Choroid / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D015237:Dinoprost / Q000378:metabolism; D015536:Down-Regulation; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D007052:Ibuprofen / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000378:metabolism; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D011465:Prostaglandins, Synthetic / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000096:biosynthesis / Q000502:physiology*; D013552:Swine; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D011450:Prostaglandin Endoperoxides, Synthetic; D011453:Prostaglandins; D011465:Prostaglandins, Synthetic; D011982:Receptors, Prostaglandin; D014662:Vasoconstrictor Agents; C034671:prostaglandin F2alpha receptor; D019335:Nitroarginine; D009569:Nitric Oxide; D013928:Thromboxane A2; C026678:carboprostacyclin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015544:Inositol 1,4,5-Trisphosphate; D015237:Dinoprost; D011464:Epoprostenol; D000242:Cyclic AMP; D006152:Cyclic GMP; D015230:Prostaglandin D2; D007052:Ibuprofen