eNOS involved in colitis-induced mucosal blood flow increase

Abstract

The role of NO in inflammatory bowel disease is controversial. Studies indicate that endothelial nitric oxide synthase (eNOS) might be involved in protecting the mucosa against colonic inflammation. The aim of this study was to investigate the involvement of nitric oxide (NO) in regulating colonic mucosal blood flow in two different colitis models in rats. In anesthetized control and colitic rats, the distal colon was exteriorized and the mucosa visualized. Blood flow (laser-Doppler flowmetry) and arterial blood pressure were continuously monitored throughout the experiments, and vascular resistance was calculated. Trinitrobenzene sulfonic acid (TNBS) or dextran sulfate sodium (DSS) was used to induce colitis. All groups were given the NOS inhibitor N(omega)-nitro-l-arginine (l-NNA) or the inducible NOS (iNOS) inhibitor l-N(6)-(1-iminoethyl)-lysine (l-NIL). iNOS, eNOS, and neuronal NOS (nNOS) mRNA in colonic samples were investigated with real-time RT-PCR. Before NOS inhibition, colonic mucosal blood flow, expressed as perfusion units, was higher in both colitis models compared with the controls. The blood flow was reduced in the TNBS- and DSS-treated rats during l-NNA administration but was not altered in the control group. Vascular resistance increased more in the TNBS- and DSS-treated rats than in the control rats, indicating a higher level of vasodilating NO in the colitis models. l-NIL did not alter blood pressure or blood flow in any of the groups. iNOS and eNOS mRNA increased in both colitis models, whereas nNOS remained at the control level. TNBS- and DSS-induced colitis results in increased colonic mucosal blood flow, most probably due to increased eNOS activity.

The Effect of N. Acetylcysteine and Ginger on Acetic Acid Induced Colitis in Adult Male Albino Rat: Histological, Immunohistochemical and Morphometric Study

“…The current results found marked up-regulation of i.NOS immunoexpression in induced colitis model accompanied by dense inflammatory cellular infiltration, mucosal and submucosal. This was in agreement with the previously reported data at mRNA levels [59,60]. Interestingly, this up-regulation was reversed with ginger treatment and not in NAC treated group.…”

Lactobacillus reuteriprevents colitis by reducing P-selectin-associated leukocyte- and platelet-endothelial cell interactions

“…We and others (16,20,40) have earlier observed that the degree of inflammation in DSS-induced colitis tends to be greater in the distal than in the proximal colon. This is confirmed here in the histological sections as well as in the P-selectin expression, which was three times higher in the distal compared with the proximal and transverse colon.…”

“…Environmental factors, such as ingestion of pathogens or chemical substances disturbing the delicate equilibrium in the intestine, as well as genetic susceptibility, have been implicated in the pathogenic mechanisms behind IBD (55). Here we have used the DSS model of colitis, which resembles UC with a diffuse mucosal inflammation covering the entire colon, resulting in diarrhea and rectal bleeding (12,31,33,40). P-selectin has been shown to be a key molecule in the pathophysiology of DSS-induced murine colitis (18,46,57).…”

Selective inhibition of iNOS attenuates trauma-hemorrhage/resuscitation-induced hepatic injury

“…This variability in the results may be due to differences in the parameters measured, the experimental models employed, and, most important, the selectivity of NOS inhibitors used (19,32). Studies have shown that N G -nitro-L-arginine methyl ester (L-NAME), a nonspecific NOS inhibitor, increases hepatic and intestinal injury following ischemia-reperfusion (I/R) (24,31).…”