Endothelium-derived nitric oxide limits sympathetic neurogenic constriction in intestinal microcirculation.

We have recently shown that endogenous nitric oxide (NO) activity can attenuate the sympathetic neurogenic constriction of intestinal arterioles. The purpose of this study was to determine whether the microvascular endothelium is an important site of NO production under these conditions. In the superfused small intestine of the rat, intravital microscopy was used to study the responses of first-order arterioles (1A) to perivascular sympathetic nerve stimulation and directly applied norepinephrine before and then after passage of a CO2 embolus through the 1A lumen to inhibit endothelial function. CO2 embolization did not significantly alter resting arteriolar diameter (50 +/- 4 microns before vs. 51 +/- 4 microns after embolization) but abolished the dilator response to acetylcholine without altering the dilator response to sodium nitroprusside. Stimulation at 3, 8, and 16 Hz caused respective constrictions of 4 +/- 1, 11 +/- 1, and 18 +/- 2 microns, and after CO2 these responses were significantly increased to 9 +/- 1, 18 +/- 1, and 29 +/- 3 microns, respectively. Exposure to the nitric oxide synthase inhibitor NG-monomethyl-L-arginine(10(-4) M in superfusate) after CO2 embolization had no further effect on the magnitude of neurogenic constriction. Similar results were seen when embolization was achieved with N2, and CO2 embolization had the same effect on norepinephrine-induced constriction as it did on neurogenic constriction. These results suggest that nitric oxide of endothelial origin can attenuate sympathetic neurogenic constriction in the intestinal microvasculature.