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Actions by angiotensin II on esophageal contractility in humans

Artikel i vetenskaplig tidskrift
Författare Anna Casselbrant
Anders Edebo
Johanna Wennerblom
Hans Lönroth
Herbert F Helander
M. Vieth
L. Lundell
Lars Fändriks
Publicerad i Gastroenterology
Volym 132
Nummer/häfte 1
Sidor 249-60
ISSN 0016-5085 (Print)
Publiceringsår 2007
Publicerad vid Institutionen för kliniska vetenskaper
Sidor 249-60
Språk en
Länkar www.ncbi.nlm.nih.gov/entrez/query.f...
Ämnesord 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
Ämneskategorier Medicin och Hälsovetenskap

Sammanfattning

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.

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