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Back to 2015 Annual Meeting Program Relieving Mechanism of Exogenous Angiotensin II, III&IV to Chronic and Refractory Constipation: Stimulating Intestinal Secretion and Motility in Human Jinping Gao2, 1, Dengping Shi1, Chenglong LI1, Weiguo Dong3, Kaixiu Wang1, Ling Jin1, Yuxing Zhang1, Bing Hu1, Hong Xia3, Xi-Yu Wang*4, Guo-Du Wang4 1Department of Surgery, Hubei Jingchu Technikon Center Hospitol), Jinmen, China; 2Surgery, Jinmen Second Hospital, Jinmen, China; 3Gastroenterology, Hubei province hospital, Wuhan, China; 4Physiology and Cell Biology, The Ohio State University, Columbus, OH Background/Aims: Angiotensin (Ang) family of renin-angiotensin system (RAS) consisted of Ang I, II III and IV. Recent evidences showed that local RAS play paracrine/ autocrine role in regulating gastrointestinal functions. Some literatures reported inconsistent results about angiotensin receptors mediated by Ang II in enteric neurons, smooth muscle and epithelium. The aim of present study is to examine neurogenic and non-neurogenic effects of Ang in intestinal behavior, epithelial secretion and muscular motility with human small intestine and colon. Methods: Wireless capsule endoscopy is used to observe human intestinal propulsion and feces movement. Ussing chamber system was used to detect short circuit current (Cl- secretion) across mucosal epithelial cells. Organ bath system was applied to record isometric tension of human intestinal strips. The human colonic specimens were obtained from 37 adult patients (19 men and 18 women) undergoing intestinal surgery. Results: The capsule endoscopy is used in 14 chronic and 8 refractory constipation patients. Bowel propulsion and feces hydration were significantly enhanced in the patients to take GX1, an Ang IV-like peptides, (10mg/day), but not in the patient to take placebo. The cardiovascular adverse events of the GX1 have not found in all patients. The results from mucosal secretion showed that application of AngII, Ang III and AngIV (0.1-100nM) elicited concentration- dependent increase of Cl- secretion in either human jejunal (n=12) or colonic (n=16) preparations. The Angs -evoked responses can be suppressed by EMD66684 (10µM), a potent selective AT1 receptor antagonist, but not by PD123319 (20µM), an AT2 receptor antagonist. The potent rank is AngII>AngIII>AngIV in the mucosal secretion. Tetrodotoxin (TTX, 1µM) suppressed significantly basic secretion, but not blocked Angs-evoked secretion. The results from organ bath recording showed that Angs (0.1-100nM) evoked significantly muscle contraction in dose dependent manner in 24 of 24 human jejunum and 16 of16 colonic preparations. Likewise, the potent rank is AngII>AngIII and AngIV in the smooth muscle contractile responses. Angs evoked the contractile responses were suppressed by pre-incubating EMD6684, but not by PD123319 and TTX. Conclusion: The results of present study showed that Angs relieved constipation through activation of AT1 receptor in intestinal mucosal and muscular cells to stimulate bowel secretion and movement. AngII, III, IV have successive potent effects in intestinal secretion and motility. The results suggested that Ang IV as an AT1 agonist and less cardiovascular effect is an important pharmaceutical molecular in relieving constipation. (Supported by The scientific research funding from Department of education, Hubei province，China. B201405) Back to 2015 Annual Meeting Program |
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