Glucose-induced intestinal hyperemia is mediated by nitric oxide

Glucose-induced absorptive hyperemia of the intestine has been well demonstrated through microsphere blood flow experiments. We have previously demonstrated that glucose, when applied topically to rat ileal epithelium, restores microvascular vessel diameters and blood flow following Escherichia coli bacteremia or hemorrhage/resuscitation. However, the mechanisms of this hyperemia are not completely understood. We hypothesize that nitric oxide is a mediator of the microvascular response to glucose exposure on the rat intestinal epithelium. Methods: Male Sprague-Dawley rats, 200-225 g, were monitored for hemodynamic stability with mean arterial blood pressure and heart rate. A 2-cm segment of the terminal ileum with intact neurovascular supply was exposed for intravital videomicroscopy. Intestinal arteriolar diameters (A1D, inflow; and A3D, premucosal arterioles) and microvascular blood flow (A1Q) were measured following topical application of isoosmotic glucose or saline, with or without L-NAME (LN, 100 mM), a competitive inhibitor of nitric oxide synthase. Statistical analysis was performed by ANOVA followed by Tukey-Kramer honestly significant difference test. Results: All data are expressed as mean percentage changes from baseline +/- standard error of the mean. Hemodynamic variables did not change during the experimental procedure and there were no significant differences among group baselines. Addition of isotonic glucose to the bath solution caused a significant increase in A3D that persisted throughout the experiment (at 30 min, 19.2 +/- 4.2 vs -3.9 +/- 4.5, P < 0.05). This vasodilation was blocked by topical administration of LN (3.1 +/- 2.9, P < 0.05). A1D remained at baseline levels (saline and glucose) or constricted (LN) in all groups. Topical LN also attenuated A1Q in both the saline and glucose groups. Conclusions: These data demonstrate that glucose-induced intestinal hyperemia is primarily characterized by premucosal A3 arteriole dilation in this model and that nitric oxide is a mediator of glucose-induced intestinal hyperemia. These findings suggest that either (1) glucose directly causes endothelial nitric oxide production or (2) epithelial cells transduce a vasodilatory signal through vascular endothelial-derived nitric oxide during postprandial intestinal hyperemia.