Abran D, Varma D R, Chemtob S
Centre de Recherche de l'Hôpital Sainte-Justine, Department of Pediatrics, Montréal, Québec, Canada.
Am J Physiol. 1997 Mar;272(3 Pt 2):R995-1001. doi: 10.1152/ajpregu.1997.272.3.R995.
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.
本研究旨在确定围产期高水平的前列腺素(PG)和血栓素(TxA2)是否会改变其脉络膜血管运动效应和受体水平。使用了来自生理盐水或布洛芬处理的1日龄仔猪的非灌注(眼杯制剂)和灌注脉络膜血管以及成年猪的组织;所有前列腺素对两种制剂都产生了相似的血管运动效应。新生仔猪脉络膜中的前列腺素F2α(PGF2α)、TxA2、前列环素(PGI2)和前列腺素D2(PGD2)水平高于成年猪;向新生仔猪注射布洛芬(每4小时40mg/kg,共48小时)可显著降低所有这些前列腺素在脉络膜中的水平。与成年猪相比,PGF2α和TxA2模拟物U-46619在新生仔猪中引起的脉络膜血管收缩和肌醇1,4,5-三磷酸(IP3)生成较少。布洛芬处理增加了脉络膜PGF2α的血管收缩效应、IP3生成和受体,但未改变对U-46619的反应。卡前列环素(PGI2类似物)在新生仔猪中引起的脉络膜血管舒张和腺苷3',5'-环磷酸腺苷(cAMP)生成比成年猪更大;这些效应未被布洛芬改变。PGD2不会增加cAMP,但在新生仔猪脉络膜中引起的舒张和亚硝酸盐[一氧化氮(NO)的氧化产物]生成比成年猪更大,布洛芬和NO合酶抑制剂N(ω)-硝基-L-精氨酸可将其降低至成年水平。这些数据表明,围产期高水平的PG会下调PGF2α受体和血管效应,但不会改变脉络膜对TxA2和PGI2的反应;NO似乎有助于PGD2的血管舒张效应。