NITRIC-OXIDE MODULATES REGIONAL BLOOD-FLOW DIFFERENCES IN THE FETAL GASTROINTESTINAL-TRACT

We studied the role of endogenous nitric oxide (NO) in the regulation of gastrointestinal (GI) circulation in 11 chronically instrumented an d unanesthetized late-gestation fetal sheep. Systemic and GI blood flo ws were measured by the radiolabeled microsphere technique. Mean arter ial pressure (MAP), heart rate, blood flows, oxygen delivery, and vasc ular resistance were determined before and after infusion of the speci fic NO synthase inhibitor, N-omega-nitro-L-arginine (L-NNA), to cumula tive doses of 10 and 25 mg/kg. At both L-NNA doses, MAP increased, and combined ventricular output and heart rate decreased. GI blood flow a nd oxygen delivery decreased and vascular resistance increased for the stomach, all segments of the small intestine, and proximal colon and cecum but were unchanged in the middle and distal colon and rectum. Be cause blood flow reduction in the small intestine was pronounced (from 176 to 107 ml . min(-1). 100 g(-1), P < 0.001) and blood flow in the large intestine was unchanged, distribution of intestinal blood flow b ecame more uniform. Overall, blood flow reduction was proportionally g reater in GI circulation than in the remainder of fetal circulation. I n three additional animals we established that L-NNA reduced blood flo w to the mucosal-submucosal layer (P < 0.02) but not to the muscularis serosa of the small intestine. In the same animals, L-arginine (250 m g/kg) restored systemic hemodynamics and partially restored small inte stinal blood flow. Our results suggest that NO is an important differe ntial regulator of vascular tone in the developing GI circulation.