The muscular expression of RAS in patients with achalasia.
BACKGROUND
Angiotensin II (AngII) elicits smooth muscle contractions via activation of AngII type 1 receptor (AT1R) in the intestinal wall and in sphincter regions in several species. Achalasia is a rare swallowing disorder and is characterized by a loss of the wave-like contraction that forces food through the oesophagus and a failure of the lower oesophageal sphincter to relax during swallowing.


OBJECTIVE
The present study was undertaken to elucidate expression and distribution of a local renin-angiotensin system (RAS) in the muscular layer of distal normal human oesophagus as well as in patients with achalasia using western blot analysis, immunohistochemistry and polymerase chain reaction (PCR).


RESULTS
AT1R, together with enzyme renin and cathepsin D expression were decreased in patients with achalasia. In contrast, the mast cells chymase, cathepsin G, neprilysin and the receptor for angiotensin 1-7 peptides, the MAS receptor, were increased in patients with achalasia.


CONCLUSIONS
The results showed the existence of a local RAS in human oesophageal muscular layer. The enzymes responsible for AngII production are different and there has been a shift in receptor physiology from AT1R to MAS receptor in patients with achalasia. These changes in the RAS might play a significant role in the physiological motor control for patients with achalasia.
Department of Gastrosurgical Research and Education, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden anna.casselbrant@gastro.gu.se.
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Casselbrant
Department of Gastrosurgical Research and Education, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
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Kostic
Department of Gastrosurgical Research and Education, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
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Lönroth
D000368:Aged; D000803:Angiotensin I / Q000378:metabolism; D016022:Case-Control Studies; D056649:Cathepsin G / Q000378:metabolism; D053818:Chymases / Q000378:metabolism; D004931:Esophageal Achalasia / Q000378:metabolism*; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008407:Mast Cells / Q000201:enzymology; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism; D012084:Renin-Angiotensin System; D016622:Silver Staining
D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D000803:Angiotensin I; D056649:Cathepsin G; D053818:Chymases; C118790:angiotensin I (1-7)
MAS receptor; Oesophagus; achalasia; angiotensin 1–7; angiotensin II; angiotensin II receptors; mast cell; muscle