Longitudinal muscle shows abnormal relaxation responses to nitric oxide and contains altered levels of NOS1 and elastin in uncomplicated diverticular disease.

OBJECTIVE: Recent evidence challenges the 'low-fibre/high-colonic intraluminal pressure' hypothesis of diverticular disease (DD) and raises the possibility that other mechanisms are involved. Although bowel wall smooth muscle is known to be hypercontractile in DD, the nature of its relaxation is unknown. The present study investigated colonic smooth muscle responses to nitric oxide, as well as the smooth muscle contents of neural nitric oxide and elastin associated with the disease. METHOD: Immunohistochemical/image analysis of antibodies to nitric oxide synthase (NOS1), co-localized with protein gene product (PGP) and to elastin, was performed on three histological sections of sigmoid colons from 20 patients (10 DD, 10 controls) following resections for rectal tumours. Organ bath experiments examined smooth muscle responsiveness to nitroprusside, a nitric oxide donor. RESULTS: Uncomplicated diverticular longitudinal muscle showed lower nitric oxide immunoreactivity compared with controls: median percentage surface area of NOS1 over PGP was 26.0% (range 0.5-58.3), controls 45.0% (35.0-70.1; P = 0.018). Median percentage surface area of elastin was elevated, 21.3% (10.6-45.6), controls 8.2% (1.7-13.5; P = 0.0002), together with a low sensitivity to nitroprusside [mean - log EC(50) 5.3 (SD 0.5), controls 6.6 (SD 0.5), difference 1.3, 95% CI 0.8-1.7; P < 0.0001] and there were lower maximum relaxation responses to nitroprusside compared with controls: median percentage (relaxation induced by nitroprussside/contraction induced by bethanecol) was 52.0%, range (20.0-92.0), controls 100.0% (71.0-125.0), P < 0.0001. No statistically significant differences were found in circular muscle, at the sample size studied. CONCLUSION: This study established, for the first time, specific abnormalities in longitudinal muscle relaxation and contents of neural nitric oxide and elastin in uncomplicated DD. These findings may have important implications for both colon structure and function in the disease.

Increased distribution of collagen type III and reduced expression of matrix metalloproteinase 1 in patients with diverticular disease.

Diverticular disease is an increasingly common clinical problem especially in Western industrialized countries, but the mechanism by which the disease develops remains unclear. Based on studies showing a structural change in the colonic wall in these patients, we examined whether there are any disorders concerning the collagen metabolism in patients with diverticular disease. Samples of colonic tissue from 13 patients with diverticulitis were compared to 14 controls. We performed a Sirius red test for the overall collagen content and immunohistochemical studies facing differentiation between collagen type I and type III and the expression of matrix metalloproteinases 1 and 13. In the bowel sections of patients with diverticulitis there were decreased levels of mature collagen type I (1.37+/- 0.32 vs. 1.59 +/- 0.31) and increased levels of collagen type III (1.61+/- 0.32 vs. 1.42 +/- 0.42), with a resulting lower collagen ratio I/III. The expression of MMP-I was reduced significantly in the diverticulitis group (4.83 +/- 0.92 vs. 6.02 +/- 1.98) while expression of MMP-13 did not differ significantly between the two groups (1.03 +/- 0.11 vs. 1.04 +/- 0.12). Our findings support the theory of structural changes in the colonic wall as one of the major pathogenic factors in the development of diverticular disease. Further studies must focus on the complex interactions of several extracellular matrix components.