Role of nitric oxide in regulation of vascular resistance in postnatal intestine.

Studies were conducted to determine whether endothelial production of nitric oxide (NO) participates in the regulation of vascular resistance in postnatal swine intestine. In vivo, intra-arterial infusion of the arginine analogue NG-monomethyl-L-arginine (L-NMMA, 10(-4) M) increased intestinal vascular resistance 34% in 3-day-old animals and 9% in 35-day-old animals (P < 0.01); similar findings were noted during infusion of 10(-3) M L-NMMA. Mechanical augmentation of gut flow rate induced intestinal vasodilation in both age groups; L-NMMA eliminated this flow-induced dilation in intestine of 3- but not 35-day-old animals. In vitro, precontracted mesenteric artery rings from both age groups relaxed to a similar extent in response to the endothelium-independent nitrovasodilator sodium nitroprusside (SNP) and the calcium ionophore A-23187; the effect of A-23187, but not SNP, was eliminated by mechanical disruption of the endothelium. Acetylcholine (ACh) and substance P (SP), agents with vascular effects that are secondary to receptor-mediated activation of NO, caused greater relaxation of rings from younger than from older animals, and this effect was attenuated by L-NMMA or methylene blue. Unstimulated accumulation of guanosine 3',5'-cyclic monophosphate (cGMP) occurred to a similar extent in vessel segments from both groups. ACh and SP increased cGMP accumulation in segments from 3- but not from 35-day-old animals. We conclude that the NO-cGMP axis participates to a greater extent in regulation of intestinal vascular resistance in 3- than in 35-day-old swine.