The complex role of hydrogen peroxide (H2O2) in acetylcholine‐induced dilation of human mucosal intestinal microvessels

We previously reported that normal mucosal intestinal microvessels dilate in an endothelium‐dependent manner to acetylcholine (Ach) with nitric oxide and cyclooxygenase products contributing approximately 80% of the dilation. Catalase, a selective H 2 O 2 dismutase abolished the remaining dilation revealing vasoconstriction similar to endothelial denudation suggesting that H 2 O 2 might be an EDHF. In the present study we determined the mechanism of H 2 O 2 ‐mediated constriction in mucosal arterioles. Arterioles (160 ± 24 μm) were dissected from normal gut specimens, cannulated and pressurized at 60 mmHg. Changes in the diameter were recorded using videomicroscopy. Exogenous H 2 O 2 dilated microvessels in a concentration‐dependent fashion (max dilation (MD) 52% + 10%, n = 7). Endothelial denudation using luminal air infusion resulted in a concentration‐dependent vasoconstriction (MD; −51% + 6%, n = 6) indicating that H 2 O 2 is not the EDHF. Both the thromboxane A 2 receptor block SQ‐29548 and the non‐selective cyclooxygenase inhibitor indomethacin converted the constriction into dilation (MD; 42% + 16%, 85% + 7%, respectively) in denuded arterioles. SQ‐29548 augmented dilation in intact microvessels (MD; 93% + 3%, p<0.05 vs. control). These data provide evidence that the endothelium plays a critical role in the response to H 2 O 2 which is not an EDHF in the mucosal gut vasculature. H 2 O 2 acts through the endothelium and vascular smooth muscle to elicit dilation and constriction simultaneously. Our data suggest an important role of thromboxane in the constriction to H 2 O 2