No abstract

Intestinal inflammation affects smooth muscle contractility contributing to altered motility, but changes to the individual smooth muscle cells are not well described. We used video microscopy to study the contractility of circular smooth muscle cells (CSMC) isolated from the rat mid-descending colon throughout the course of TNBS-induced colitis, measuring their shortening response to carbachol (CCh), 5-HT, histamine or high K(+). In control CSMC, CCh caused a maximal shortening response of 28 (2%), similar to that for 5-HT of 27 (1%), but by day 4 of colitis, these responses were decreased by 35% and 37%, respectively. By day 36, all aspects of cholinergic contraction returned to control levels, while 5-HT-induced contraction remained significantly attenuated. In contrast, the contractile responses to histamine remained similar at all time points. K(+)-induced contraction was impaired only on day 4, and the maximal response remained substantially greater than CCh or 5-HT. Colitis caused a 121% increase in CSMC length by day 2 that persisted through day 36, independent evidence for phenotypic change. We conclude that impaired CSMC contractility at both the receptor and non-receptor levels contribute to altered smooth muscle function during colitis. Persistent changes in contractile response remained detectable after resolution of inflammation, and similar events may occur in post-enteritis syndromes seen in humans.

No abstract

Acid-induced esophagitis is associated with sustained longitudinal smooth muscle (LSM) contraction and consequent esophageal shortening. In addition, LSM strips from opossums with esophagitis are hyper-responsive, while the circular smooth muscle (CSM) contractility is impaired. To determine the origin of these changes, studies were performed on esophageal smooth muscle cells isolated from opossum esophagi perfused intraluminally on 3 consecutive days with either saline (control; n = 8) or HCl (n = 9). CSM and LSM cells, obtained by enzymatic digestion, were exposed to various concentrations of carbachol (CCh) and fixed. CCh induced concentration-dependent contraction of both LSM and CSM cells. CCh-induced LSM cell contraction was not different between control and esophagitis animals; however, there was marked attenuation in the CCh-induced contraction of CSM cells from esophagitis animals. Morphological studies revealed significant hypertrophy of the CSM cells. These findings suggest that impaired CSM contractility can be attributed at least in part to alterations to the CSM cell itself. In contrast, hyper-contractility demonstrated in LSM strips is likely related to factors in the surrounding tissue.