Alterations in intestinal contractility during inflammation are caused by both smooth muscle damage and specific receptor-mediated mechanisms

Abstract

Aim: To evaluate motoric intestinal disturbances during inflammation with Trichinella spiralis in rats as an experimental model.

Methods: We examined the changes in worm-positive (jejunum) and worm-free (ileum) intestinal segments of rats infected with T. spiralis. To investigate the relationship between structural and functional changes in smooth muscle, we measured the thickness of the muscle layers of rat jejunum and ileum. Mechanical responses to KCl 30 mmol/L, acetylcholine (ACh) 10(-8)-10(-4) mol/L, substance P (SP) 10(-9)-10(-5) mol/L, and to electrical field stimulation of longitudinal muscle strips in the jejunum and ileum were studied in muscle bath as controls (day 0) and on day 2, 6, 14, 23, and 72 after infection.

Results: After T. spiralis infestation, an inflammation of the mucosal and submucosal layers of jejunum was observed, whereas in the worm-free ileum there was not any inflammatory infiltrate. Increase in the smooth muscle thickness of both jejunum and ileum were correlated with increased responses to depolarizing agent KCl and to ACh. However, responses to SP were decreased on day 14-23 after infection in jejunum and from day 6-14 after infection in ileum. Electric field stimulation-induced contractions were transiently decreased in the jejunum (day 2 after infection) but in the ileum the contractile responses were decreased until the end of the study period.

Conclusions: Alterations in intestinal smooth muscle function do not require the presence of the parasite and the absence of histopathological signs of inflammation do not warrant intact motor function. Changes in motor responses after T. spiralis infection are not only due to smooth muscle damage but also to disturbances in specific receptor-mediated mechanisms.

Figure 1

Thickness of longitudinal and circular muscle layer of jejunum (A) and ileum (B) under controlled conditions and at different times after infection. Data collected from 6 animals are expressed as means±SEM (µm); *P<0.05, †P<0.01, ‡P<0.001 indicate differences between healthy and Trichinella spiralis-infected rats.

Figure 2

Responses of the jejunum (A) and ileum (B) to 30 mmol/L KCl-induced contraction (open column), E_max(g) response to acetylcholine (ACh; closed column) and E_max(g) response to substance P (SP; gray column) in healthy (control) and T. spiralis-infected rats. Data collected from 7 animals are expressed as a mean±SEM (g). *P<0.05, †P<0.01, and ‡P<0.001 indicate differences between healthy and Trichinella spiralis-infected rats.

Figure 3

Correlation between full muscle thickness (µm) and KCl (solid line with square symbols), acetylcholine (ACh; dashed line with triangle symbols) and substance P (SP; dotted line with circle symbols) response (g) of the jejunum (A), and the ileum (B). Correlation is present between muscle thickness, KCl and ACh response, and absent in case of SP.

Figure 4

Time-course of responses to acetylcholine (ACh) and substance P (SP) with KCl as a reference response (%RR) from the jejunum (dashed lines with circle symbols) and ileum (solid lines with square symbols). Upper panels show the changes in E_max values, expressed in percentage of KCl-induced reference response (%RR), and lower panels show the evolution of pD₂, induced by ACh and SP. Data collected on 7 animals are presented as mean±SEM. *P<0.05, †P<0.01, and ‡P<0.001 indicate differences between healthy (control) and Trichinella spiralis-infected rats.

Figure 5

Contractile responses of the jejunum (A) and ileum (B) preparations to electrical field stimulation (40 V, 10 Hz, 0.3 ms, 15 s) under controlled (closed bars) or non-adrenergic non-cholinergic conditions (NANC; open bars) by addition of atropine, phentolamine, and propranolol, each at 10⁻⁶ mol/L, added 10 minutes earlier. Data collected from 7 animals are presented as mean±SEM and expressed in percentage of 30 mmol/L KCl-induced reference response (%RR). *P<0.05, †P<0.01, and ‡P<0.001 indicate differences between healthy (control) and Trichinella spiralis-infected rats.