Is nitric oxide and heparin treatment justified in inflammatory bowel disease? An experimental study

Abstract

Microcirculatory disturbances of the colon may contribute to the pathogenesis of inflammatory bowel disease. The aim of the study was to investigate the alterations of rectal blood perfusion in experimental colitis with reference to nitric oxide and heparin treatment. The study was carried out on 36 rats, divided into six groups: group I, control; group II, control + NG-nitro-L-arginine (L-NNA); group III, colitis without treatment; group IV, colitis + L-arginine; group V, colitis + L-NNA; group VI, colitis + heparin treatment. Experimental colitis was induced by 4% acetic acid enema, and 48 h after the enema, besides the measurement of rectal capillary blood flow by means of laser Doppler flowmetry, the serum interleukin-6 (IL-6) level and histopathological alterations within the rectal mucosa were examined. Experimental colitis resulted in a drop in rectal wall perfusion. L-Arginine and heparin treatment improved the microcirculatory values. The highest IL-6 level and the most advanced histopathological alterations were observed in the rats treated with L-NNA. L-Arginine treatment had no influence on IL-6 concentration, however it aggravated the inflammatory changes within the rectal mucosa. Heparin administration reduced the IL-6 values and also had a positive impact on the microscopic alterations within the rectal wall. It is concluded that heparin treatment has a beneficial effect on the microcirculatory disturbances and inflammatory changes observed in experimental colitis. The inhibition of nitric oxide-synthase aggravated the course of experimental colitis. L-Arginine administration improves the rectal blood flow but aggravates the histopathological alterations within the rectal wall.

Changes in Distribution of Three Isoforms of Nitric Oxide Synthase in Ulcerative Colitis

“…Expression of NOS-2 in the colon epithelium, particularly in the apical region, in UC is compatible with some protective function of NOS for the injured epithelium. This idea is supported, on one hand, by development of exacerbated UC in NOS-2-de cient mice (33) or in mice treated with NOS-2 inhibitor (34), and, on the other hand, enhanced antiin ammatory effect of the NO-releasing derivative of 5-ASA (35). Induction of NOS-2 in the apical epithelium may also be a cause for inhibited bacterial invasion in UC (36).…”

Inducible nitric oxide synthase: a little bit of good in all of us

“…However, a more comprehensive review of the literature reveals that the results of NOS inhibition in the TNBS model are not all 100% protective. Studies range from almost complete protection (100%)16 21 to partial protection,15 19selective regional protection,22 no protection9, and exacerbation of injury 2324 For example, unlike the generalised inhibition of inflammation reported by some investigators, Hogaboam and colleagues22 reported that inhibition of NOS in TNBS induced colitis dramatically reduced neutrophil and macrophage infiltration into the intestine and intestinal hyperplasia (by >90%) but failed to reduce anorexia, smooth muscle hypertrophy, or myenteric nerve dysfunction.…”

Key role of mast cells and their major secretory products in inflammatory bowel disease

“…The ability of heparin to inhibit neutrophil activation, adhesion, and chemotaxis was also found in a mouse model of inflammatory bowel disorder [130,131] , suggesting that balanced interactions between mast cells and neutrophils might be important for the development of IBD. In rat models of IBD, heparin revealed its ability to attenuate TNFα induced leucocyte rolling and CD11b dependent adhesion [132] , reduce serum IL-6 level and improve microcirculatory disturbance in rectal walls [133,134] . Thus, preformed mast cell mediators seemed to have dual actions on the pathogenesis of IBD.…”