Acquired microvascular dysfunction in inflammatory bowel disease: loss of nitric oxide-mediated vasodilation

Colonic blood flow responses in experimental colitis: time course and underlying mechanisms

“…Although the papaverine data suggest that decreased smooth muscle responsiveness may account for only a small portion of the colitis-induced decline in arteriolar function, it is likely that the endothelium plays a far more significant role in the impaired vasodilation observed in this model of inflammation. The impaired endothelium-dependent vasodilatory responses to bradykinin observed in DSS-treated mice are consistent with a recent report by Hatoum and co-workers (13), who showed that, whereas normal arterioles from human intestinal submucosa dilate in a dose-dependent and endothelium-dependent manner to acetylcholine, arterioles in the chronically inflamed intestine show a significantly reduced dilation response to acetylcholine. They suggested that this defective arteriolar response accounts for the reduced colonic blood perfusion that occurs during the late remodeling stage of human IBD.…”

“…There is evidence to support a role for superoxide in mediating the altered arteriolar responses observed in human IBD. Hatoum et al (13) demonstrated that arterioles in the inflamed human colon exhibited an enhanced oxidative stress (compared with control arterioles) and that treatment with a SOD mimetic restored the acetylcholineinduced arteriolar dilation response within the inflamed human intestine. The findings of the present study indicate that the diminished responsiveness of arterioles to endothelium-dependent vasodilators that accompanies human IBD can be recapitulated in the DSS model of murine colitis and that the same mechanism may explain the defective dilatory responses of colonic arterioles in both human and murine IBD.…”

“…Although arterioles from normal human intestinal submucosa were shown to dilate in a dose-dependent and endothelium-dependent manner to acetylcholine, similar-sized arterioles in the chronically inflamed intestine exhibited a significantly reduced dilation response to acetylcholine. A role for oxidative stress was proposed in the inflammation-induced impairment of endothelium-dependent vasodilation because the inflamed arterioles exhibited an enhanced oxidative stress (compared with control arterioles), and treatment with a superoxide dismutase (SOD) mimetic restored the acetylcholineinduced vasodilatory response in arterioles within the inflamed human intestine (13). These findings suggest that superoxidedependent impairment of the dilatory capacity of arterioles may explain the reduction of tissue perfusion and oxygenation that has been detected in the chronically inflamed bowel.…”

“…However, the results of a recent study (13) provide novel insight into a mechanism that could explain the reduction in blood flow that is observed in the late remodeling stage of human IBD. Although arterioles from normal human intestinal submucosa were shown to dilate in a dose-dependent and endothelium-dependent manner to acetylcholine, similar-sized arterioles in the chronically inflamed intestine exhibited a significantly reduced dilation response to acetylcholine.…”

Immune Regulation by Microvascular Endothelial Cells: Directing Innate and Adaptive Immunity, Coagulation, and Inflammation

“…The endothelium promotes gut inflammation through comparable mechanisms. Compared with normal mucosa, microvessels in chronically inflamed mucosa show major functional alterations in inflammatory bowel disease: the microvasculature is greatly expanded, displays an abnormal architecture, adheres more leukocytes, intimately interacts with platelets, is procoagulant and angiogenic, and has an impaired NO-mediated relaxation response, all features reflecting an active input of mucosal ECs in disease pathogenesis (96). Similar endothelial dysfunctions are found in other immune/inflammatory disorders, such as diabetes, atherosclerosis, and chronic lung disease.…”