Endothelin-mediated vasoconstriction in postischemic newborn intestine

We previously suggested that the profound, sustained vasoconstriction noted in 3-day-old swine intestine after a moderate episode of ischemia-reperfus ion (I/R) reflects the unmasking of underlying constrictor tone consequent to a loss of endothelium-derived nitric oxide (NO). In this study, we sough t to determine whether endothelin-1 (ET-1) was the unmasked constrictor and whether selective loss of endothelial ETB receptors, which mediate NO-base d vasodilation, participated in the hemodynamic consequences of I/R in newb orn intestine. Studies were performed in innervated, autoperfused intestina l loops in 3- and 35-day-old swine. Selective blockade of ETA receptors wit h BQ-610 had no effect on hemodynamics under control conditions; however, w hen administered before and during I/R, BQ-610 significantly attenuated the post-I/R vasoconstriction and reduction in arteriovenous O-2 difference in the younger group. In 3-day-old intestine, reduction of intestinal O2 upta ke to a level similar to that noted after I/R by lowering tissue temperatur e had no effect on the response to BQ-610 or ET-1, indicating that the chan ge in response to BQ-610 noted after I/R was not simply consequent to the r eduction in tissue O2 demand. In studies in mesenteric artery rings suspend ed in myographs, we observed a leftward shift in the dose-response curve fo r ET-1 after selective blockade of ETB receptors with BQ-788 in 3- but not 35-day-old swine. Rings exposed to I/R in vivo behaved in a manner similar to control rings treated with BQ-788 or endothelium-denuded non-I/R rings.