This laboratory has previously reported that sustained reduction of blood flow 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 loss of endothelial nitric oxide (NO) production. This study examines the effects 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 ~50% of baseline) for 30 min or 5 h. Thereafter, they were removed to an extracorporeal perfusion circuit for in vitro hemodynamic assessment; alternatively, the mesenteric artery perfusing the gut loop was removed and cut into rings for assessment of isometric tension development. Gut loops from 3-day-old subjects exposed to low-flow conditions demonstrated significantly increased contractile responses to ANG II, NE, and ET-1; also, mesenteric artery rings from these gut loops demonstrated a significant reduction of the ED₅₀ for all three agonists. Similar changes were not observed in intestine or mesenteric artery rings from older subjects. Sustained blockade of endogenous NO synthesis with N^G-monomethyl- L-arginine duplicated the effects of exposure to sustained low-flow perfusion. It appears that sustained reduction of blood flow 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.

newborn; nitric oxide; angiotensin II; norepinephrine; endothelin-1; intestinal blood flow

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				C. A. Nankervis and P. T. Nowicki Role of endothelin-1 in regulation of the postnatal intestinal circulation Am J Physiol Gastrointest Liver Physiol, March 1, 2000; 278(3): G367 - G375. [Abstract] [Full Text] [PDF]