title: Actions by angiotensin II on esophageal contractility in humans.
abstract: OBJECTIVE
  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.affiliation: Department of Gastrosurgical Research, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. anna.casselbrant@gastro.gu.se
authors.forename: Anna
authors.initials: A
authors.lastname: Casselbrant
authors.forename: Anders
authors.initials: A
authors.lastname: Edebo
authors.forename: Johanna
authors.initials: J
authors.lastname: Wennerblom
authors.forename: Hans
authors.initials: H
authors.lastname: Lönroth
authors.forename: Herbert F
authors.initials: HF
authors.lastname: Helander
authors.forename: Michael
authors.initials: M
authors.lastname: Vieth
authors.forename: Lars
authors.initials: L
authors.lastname: Lundell
authors.forename: Lars
authors.initials: L
authors.lastname: Fändriks
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000808:Angiotensinogen / Q000235:genetics; D001562:Benzimidazoles / Q000008:administration & dosage; D001713:Biphenyl Compounds; D049630:Esophageal Sphincter, Lower / Q000502:physiology*; D004947:Esophagus / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008365:Manometry; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D010528:Peristalsis / Q000187:drug effects; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism; D012083:Renin / Q000235:genetics / Q000378:metabolism; D013777:Tetrazoles / Q000008:administration & dosage; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000808:Angiotensinogen; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D012083:Renin; C081643:candesartan