The Effects Of TRPV1and CGRP On The Contraction Of Isolated Intestinal Smooth Muscle In Septic Rats

OBJECTIVE To investigate the effects of TRPV1and CGRP on the gastrointestinalmotor disorders by isolated intestinal smooth muscle motion tests in septic rats.METHODS Forty male Sprague-Dawley（SD）rats were randomly divided into fourgroups (10rats/group): sham control (S group), sepsis (LPS group), sepsis+TRPV1receptor blocker (LT group) and sepsis+CGRP receptor blocker group (LC group).Endotoxemic rat model was induced by intraperitoneal injection of lipopolysaccharide(LPS,10mg/kg). Capsazepine (15mg/kg) was intraperitoneally injected at an hourbefore modeling in LT group, and CGRP8-37(100ug/kg) was performed a peritonealinjection at10min before in LC group. After24hours of modeling, all rats wereeuthanized by a cervical dislocation, and intestinal muscle samples were prepared invitro. Tensions, spontaneous contraction curves of intestinal smooth muscles and itsreactivity changes to different concentrations of Ach were recorded in vitro aspharmacological experiments, and degrees of inflammation were assessed using a GSscore as morphological studies.RESULTS Compared with the S group, amplitudes and frequencies of spontaneousmovement in intestinal smooth muscles and its reactivity changes to differentconcentrations of Ach were significantly decreased（P<0.05）, howerver, cycles, and GSscores were increased in LPS, LT and LC group（P<0.05）. Amplitudes of spontaneousmovement and reactivity changes to Ach (1×10-6~1×10-4mol/L) were increased （P<0.05）, while GS scores were decreased（P<0.05）and intestinal inflammation hadbeen reduced（P<0.05） in the LT and LC groups than in the LPS group. There was nostatistical difference in frequencies. The maximum values and absorption rates todifferent concentrations of Ach had a decreasing trend (P <0.05) among the threegroups.CONCLUSION These results suggest that the mechanisms of endotoxemia causedintestinal motor dysfunctions may potentially involved in CGRP and TRPV1-mediatedcapsaicin-sensitive afferent pathways, therefore overactivation of TRP channels waseffectively blocked by pretreated with its specific inhibitor Capsazepine and CGRP8-37,which can alleviated endotoxemia-induced intestinal motility dysfunctions andinflammatory bowel injuries to some extent and as a potential protective factor for theintestinal motility.