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 and unanesthetized late-gestation fetal sheep. Systemic and GI blood flows were measured by the radiolabeled microsphere technique. Mean arterial pressure (MAP), heart rate, blood flows, oxygen delivery, and vascular resistance were determined before and after infusion of the specific NO synthase inhibitor, N omega-nitro-L-arginine (L-NNA), to cumulative 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 and 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. Because 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 became more uniform. Overall, blood flow reduction was proportionally greater in GI circulation than in the remainder of fetal circulation. In three additional animals we established that L-NNA reduced blood flow 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 mg/kg) restored systemic hemodynamics and partially restored small intestinal blood flow. Our results suggest that NO is an important differential regulator of vascular tone in the developing GI circulation.