Mechanism of prevention by capsaicin of ethanol-induced gastric mucosal injury--a study in the rat using intravital microscopy.
BACKGROUND
Capsaicin acts specifically on primary afferent neurones to release neuropeptides, including calcitonin gene-related peptide (CGRP), and prevents ethanol-induced mucosal injury.


OBJECTIVE
To investigate the microvascular changes in the gastric mucosa in response to ethanol using intravital microscopy to elucidate the mechanism of capsaicin-induced gastroprotection.


METHODS
The posterior gastric wall in the rat was secured in an observation chamber and perfused with Tyrode's solution. The microcirculation was observed through a window made by removing a limited area of smooth muscle.


RESULTS
Ethanol (50%) applied to the mucosa constricted the collecting venules and venules but dilated arterioles. The constriction of the collecting venules resulted in mucosal congestion, which caused mucosal injury. Application of capsaicin to the mucosa dilated the arterioles but not the collecting venules or venules. Arteriolar dilation was inhibited by a CGRP antagonist, CGRP-(8-37). Prior application of capsaicin prevented ethanol-induced constriction of the collecting venules, and the action of capsaicin was inhibited by prior application of CGRP-(8-37).


CONCLUSIONS
The results suggest that the inhibition of ethanol-induced gastric injury by capsaicin is attributable to the suppression of collecting venule constriction, via CGRP release.
Saeki
T
T
Department of Internal Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Ohno
T
T
Boku
K
K
Saigenji
K
K
Katori
M
M
Majima
M
M
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000009:adverse effects* / Q000494:pharmacology; D046508:Culture Techniques; D019610:Cytoprotection; D000431:Ethanol / Q000009:adverse effects* / Q000494:pharmacology; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008833:Microcirculation; D051381:Rats; D017207:Rats, Sprague-Dawley
D002492:Central Nervous System Depressants; D000431:Ethanol; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin