Actions by angiotensin II on esophageal contractility in humans

• 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.

Nyckelord

Aged

Aged

80 and over

Angiotensin II/*pharmacology

Angiotensin II Type 1 Receptor Blockers/administration & dosage

Angiotensinogen/genetics

Benzimidazoles/administration & dosage

Esophageal Sphincter

Lower/*physiology

Esophagus/*physiology

Female

Gene Expression

Humans

Male

Manometry

Middle Aged

Muscle Contraction/*drug effects

Peptidyl-Dipeptidase A/genetics

Peristalsis/drug effects

Receptor

Angiotensin

Type 1/genetics/metabolism

Receptor

Angiotensin

Type 2/genetics/metabolism

Renin/genetics/metabolism

Tetrazoles/administration & dosage

Vasoconstrictor Agents/*pharmacology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)