BACKGROUND & AIMS:Angiotensin II is a potent activator of smooth muscles but has not been much investigated with regard to gastrointestinal motor activity. This study explores expression of the renin-angiotensin system (RAS) in human esophageal musculature and actions by Angiotensin II both in vitro and in vivo. METHODS: Muscular specimens of esophageal body and lower esophageal sphincter were obtained from patients undergoing resection as a result of mucosal neoplasm. Healthy volunteers participated in functional examinations of esophageal motility assessed by high-resolution manometry and multiple transmucosal potential-difference measurements. RESULTS: Gene transcripts of key components of RAS were found in the esophageal musculature. Immunohistochemistry revealed a distinct staining for Angiotensin II type 1 (AT(1)) receptors in the muscular bundles and blood-vessel walls, whereas Angiotensin II type 2 receptors were confined to blood vessels only. Angiotensin II caused concentration-dependent contractions in vitro, which were inhibited by the AT(1) receptor antagonist losartan but not by the Angiotensin II type 2 receptor antagonist PD123319. Administration of the AT(1) receptor antagonist candesartan reduced the amplitude of swallow-induced peristaltic contractions and both the length and pressure amplitude of baseline high-pressure zone at the esophagogastric junction. Neither swallow-induced axial movements, nor the contraction after transient lower esophageal sphincter relaxations, were influenced by candesartan pretreatment. CONCLUSIONS: The study demonstrates a local RAS in the musculature of the distal esophagus and that Angiotensin II is a potent stimulator of esophageal contractions via the AT(1) receptor. The results suggest that Angiotensin II participates in the physiological control of the human esophageal motor activity.
RCT Entities:
BACKGROUND & AIMS:Angiotensin II is a potent activator of smooth muscles but has not been much investigated with regard to gastrointestinal motor activity. This study explores expression of the renin-angiotensin system (RAS) in human esophageal musculature and actions by Angiotensin II both in vitro and in vivo. METHODS: Muscular specimens of esophageal body and lower esophageal sphincter were obtained from patients undergoing resection as a result of mucosal neoplasm. Healthy volunteers participated in functional examinations of esophageal motility assessed by high-resolution manometry and multiple transmucosal potential-difference measurements. RESULTS: Gene transcripts of key components of RAS were found in the esophageal musculature. Immunohistochemistry revealed a distinct staining for Angiotensin II type 1 (AT(1)) receptors in the muscular bundles and blood-vessel walls, whereas Angiotensin II type 2 receptors were confined to blood vessels only. Angiotensin II caused concentration-dependent contractions in vitro, which were inhibited by the AT(1) receptor antagonist losartan but not by the Angiotensin II type 2 receptor antagonist PD123319. Administration of the AT(1) receptor antagonist candesartan reduced the amplitude of swallow-induced peristaltic contractions and both the length and pressure amplitude of baseline high-pressure zone at the esophagogastric junction. Neither swallow-induced axial movements, nor the contraction after transient lower esophageal sphincter relaxations, were influenced by candesartan pretreatment. CONCLUSIONS: The study demonstrates a local RAS in the musculature of the distal esophagus and that Angiotensin II is a potent stimulator of esophageal contractions via the AT(1) receptor. The results suggest that Angiotensin II participates in the physiological control of the human esophageal motor activity.
Authors: Sarah E Sansom; Gerard J Nuovo; Mickey M Martin; Sainath R Kotha; Narasimham L Parinandi; Terry S Elton Journal: Am J Physiol Gastrointest Liver Physiol Date: 2010-06-17 Impact factor: 4.052
Authors: Kenneth E Bernstein; Frank S Ong; Wendell-Lamar B Blackwell; Kandarp H Shah; Jorge F Giani; Romer A Gonzalez-Villalobos; Xiao Z Shen; Sebastien Fuchs; Rhian M Touyz Journal: Pharmacol Rev Date: 2012-12-20 Impact factor: 25.468
Authors: Peter Hallersund; Herbert F Helander; Anna Casselbrant; Anders Edebo; Lars Fändriks; Anders Elfvin Journal: BMC Gastroenterol Date: 2010-01-14 Impact factor: 3.067