Efecto de los isoprostanos en la reactividad vascular pulmonar y sistémica durante el período neonatal.
SUMMARY: "Effects of Isoprostanes in Pulmonary and Sistemic Vascular Reactivity during Neonatal Period". BACKGROUND: Isoprostanes are prostaglandin (PG)-like compounds produced non enzymatically by free radical-catalyzed peroxidation of arachidonic acid. The vascular effects of these compounds in neonatal vasculature are poorly known. OBJECTIVE: We aimed to study the effects of several E-ring and F-ring isoprostanes on mechanical activity in pulmonary arteries (PA), pulmonary veins (PV) and in mesenteric arteries (MA) from newborn and 2-week-old piglets. DESIGN/METHODS: The contractile and relaxant responses to 8-iso PGE1, 8-iso PGE2, 8-iso PGF1?, 8-iso PGF1?, 8-iso PGF2?, 8-iso PGF2?, and the thromboxane A2 mimetic U46619 were studied using organ bath techniques. RESULTS: Isoprostanes produced powerful concentration-dependent contractions of PA, PV and MA. Neonatal PA were more sensitive to 8-iso PGE2, 8-iso PGF1?, 8-iso PGF1? and 8-iso PGF2? than 2- week-old PA, but a clear ontogenic pattern was not observed for the rest of the compounds. Neonatal PV were more sensitive to 8-iso PGE2 and 8-iso PGF1?, and neonatal MA were more sensitive to 8-iso PGE2, 8-iso PGF1?, 8-iso PGF2? and 8-iso PGF2? than the corresponding 2-week-old vessels. The sensitivity to U46619-decraesed with postnatal age in MA but did not change in PA and PV. The contractile responses to all the isoprostanes and to U46619 were reverted by the thromboxane A2 receptor (TP) antagonist SQ 29,548. Moreover, isoprostanes-evoked contractions were blocked by inhibitors of tyrosine kinase (genistein) and Rho kinase (Y 27632 and hydroxy-fasudil). 8-iso-PGE2 induced modest dose-dependent relaxations (maximal relaxation of 60.1±8,7%) in 2-week-old PA. In CA, 8-iso PGE2 was the most potent vasodilator but relaxant responses evoked by 8-iso PGE1 y 8-iso PGF2? were also observed. 8-iso PGE2 -evoked PA relaxation was markedly impaired by the nitric oxide (NO) synthase inhibitor L-NAME and the soluble guanylate cyclase inhibitor ODQ. Misoprostol, PGE1 and PGE2 fully relaxed U46619-contracted PA, while no relaxation was observed in response to PGD2 or iloprost. CONCLUSIONS: 1. Isoprostanes produce constriction of neonatal porcine pulmonary and mesenteric vascular smooth muscle which involve TP receptors coupled to tyrosine kinases and Rho kinases. 2. Isoprostanes produce modest or absent relaxant responses in piglet vascular smooth muscles. 8-iso-PGE2-evoked relaxation of piglet PA is likely to be mediated by NO.
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Advisor:Villamor zambrano, Eduardo; Jiménez González, Rafael
School:Universitat de Barcelona
Source Type:Master's Thesis
Keywords:obstetrícia i ginecologia pediatria radiologia medicina física
Date of Publication:11/25/2005