Major Vasodilator Role for Nitric Oxide in the Gastrointestinal Circulation of the Mid-Gestation Fetal Lamb

Abstract

As nitric oxide (NO) may be a particularly important vasodilator in early life, we investigated its role in the regulation of the gastrointestinal (GI) circulation at mid-gestation. Cardiac output and GI blood flow were measured by the radioactive microsphere technique in eight chronically instrumented and unanesthetized mid-gestation fetal sheep. Mean arterial pressure (MAP), heart rate, blood flow, oxygen delivery, and vascular resistance were determined before and after infusion of the specific NO synthase inhibitor, Nomega-nitro-L-arginine (L-NNA) at doses of 10 and 25 mg/kg. In response to L-NNA infusion, MAP increased (p < 0.01) and combined ventricular output decreased (p < 0.001). GI blood flow and oxygen delivery decreased and vascular resistance increased in the stomach and all segments of the small and large intestine (all p < 0.001). The greatest reduction in blood flow was in the small intestine (p < 0.01) and the basal differential pattern of small intestinal blood flow exceeding large intestinal flow was completely abolished. These changes were much greater than those previously described in late-gestation fetuses. Our results suggest that, at mid-gestation, NO plays a major role in the regulation of blood flow and vascular tone across all segments of the fetal GI tract, with its effects being more pronounced than later in development.

Plasma Cyclic Guanosine Monophosphate Reflecting the Severity of Persistent Pulmonary Hypertension of the Newborn

“…We found no differences in the response in PAP/SAP or in oxygenation index between preterm and term infants. This finding is in accordance with previous experimental studies: Even in the mid-gestational fetal lamb a specific NO inhibitor affects mean arterial pressure [9], and in the premature ovine pulmonary circulation, pulmonary vascular resistance is modulated by endogenous NO [10]. In clinical studies in preterm infants, NO improved oxygenation but did not improve survival [11,12].…”

Fetal and postnatal ovine mesenteric vascular reactivity

“…However, the vasodilator NO pathways appear to be functional at this gestation ( Figure 2 ). Similarly, NO-dependent basal intestinal flow has been demonstrated in vivo in 92- to 100-d GA ovine fetuses (27). …”

“…Simultaneously, there is a decrease in basal NOS activity with no increase in eNOS protein. Infusion of LNA to fetal lambs results in approximately 40% decrease in small intestinal blood flow in late gestation lambs compared with approximately 57% decrease (by 73 ml/kg/min/100 g) in mid-gestation lambs also suggesting lower basal NOS activity at late gestation (27,28). This late-preterm GA is associated with the highest imbalance between mediators of constriction and relaxation favoring the former.…”

“…This period also corresponds to rapid increase in intestinal blood flow. In vivo studies showed a substantial increase in small intestinal blood flow from 127 ± 11 to 176 ± 11 ml/kg/min/100 g from 92- to 100-d gestation to 128- to 139-d gestation in lambs (27,28). …”

Metabolic response of porcine colon explants to in vitro infection by Brachyspira hyodysenteriae: a leap into disease pathophysiology

“…2). NO exerts a range of functions in the gastrointestinal tract, acting as a pro-inflammatory stimulus, stimulating mucus secretion, opening chloride channels in the colon and promoting vasodilation (Brown et al 1992; Tamai and Gaginella 1993; Fan et al 1998). In addition, other authors have shown that citrulline alone induces endothelial relaxation as it enhances the production of NO, probably due to its recycling into arginine (Raghavan and Dikshit 2001).…”