Role of endothelin-1 in regulation of the postnatal intestinal circulation

Newborn intestine is uniquely prone to vasoconstriction in response to a wi de variety of perturbations. To test the hypothesis that endothelin (ET)-1 is an important factor in this process, we determined the effects of exogen ous ET-1 administration and blockade of endogenous ET-1 in vivo and in vitr o in 3- and 35-day-old swine. Intramesenteric artery administration of exog enous ET-1 to vascularly isolated in vivo gut loops (10(-9) M/kg bolus) cau sed vasoconstriction and reduced gut Oz uptake similarly in these age group s. Selective blockade of ETA or ETB receptors with BQ-610 or BQ-788, respec tively, in vascularly isolated in vivo gut loops had no effect on gut vascu lar resistance or Oz uptake in either age group; within in vitro gut loops, BQ-610 significantly increased vasoconstriction when perfusion pressure wa s reduced below baseline, but only in 3-day-old animals; i.e., it impaired the autoregulatory response to perfusion pressure reduction. Exogenous ET-1 significantly decreased capillary perfusion within in vitro gut loops, as evidenced by a decrease in capillary filtration coefficient, but only in S- day-old animals; furthermore, blockade of endogenous ET-1 activity with BQ- 610 significantly enhanced capillary filtration coefficient in 3-day-old an imals and increased O-2 extraction ratio. ET-1 did not depress intestinal m etabolic rate, as evidenced by its effect on the O-2 uptake-blood flow rela tionship; it did compromise tissue oxygenation because of its effects on in testinal O-2 transport. ET-1 concentration in mesenteric venous effluent ex ceeded arterial concentration, but only in 8-day-old intestine, suggesting production of ET-1 by newborn intestine. We conclude that ET-1 exerts an ag e-dependent effect on intestinal hemodynamics in postnatal intestine, havin g a greater impact in 3- than in 35-day-old intestine.