Effects of sustained low-flow perfusion on the response to vasoconstrictoragents in postnatal intestine

This laboratory has previously reported that sustained reduction of blood f low in newborn intestine causes a triphasic increase in vascular resistance that occurs over 3-4 h and that these changes are mediated, in part, by lo ss of endothelial nitric oxide (NO) production. This study examines the eff ects of exposure to sustained low-flow perfusion on the subsequent response to three contractile agonists: ANG II, norepinephrine (NE), and endothelin -1 (ET-1). Gut loops from 3- and 35-day-old swine were exposed to low-flow conditions in vivo (i.e., reduction of flow to similar to 50% of baseline) for 30 min or 5 h. Thereafter, they were removed to an extracorporeal perfu sion circuit for in vitro hemodynamic assessment; alternatively, the mesent eric artery perfusing the gut loop was removed and cut into rings for asses sment of isometric tension development. Gut loops from 3-day-old subjects e xposed to low-flow conditions demonstrated significantly increased contract ile responses to ANG II, NE, and ET-1; also, mesenteric artery rings from t hese gut loops demonstrated a significant reduction of the ED50 for all thr ee agonists. Similar changes were not observed in intestine or mesenteric a rtery rings from older subjects. Sustained blockade of endogenous NO synthe sis with N-G-monomethyl-L-arginine duplicated the effects of exposure to su stained low-flow perfusion. It appears that sustained reduction of blood fl ow in newborn intestine decreases constitutive NO production, which in turn causes a generalized enhancement of the contractile efficacy of ANG II, NE , and ET-1.