Reduced adrenomedullin expression in gastric mucosa of portal hypertensive rats after ethanol-induced injury.
OBJECTIVE
To determine the expression and localization of adrenomedullin (AM) and its receptor (AM-R) in portal hypertensive (PHT) gastric mucosa after intragastric ethanol administration.


BACKGROUND
The repair of gastric mucosal injury requires reestablishment of the microvascular network. The authors previously demonstrated impaired angiogenesis of PHT gastric mucosa after ethanol-induced injury. Because AM, a potent vasodilatory peptide, is also a novel growth and angiogenic factor, the authors hypothesized that AM is involved in the impaired repair of PHT gastric mucosa and its microvasculature after damage.


METHODS
Either PHT or sham-operated rats received intragastrically 100% ethanol, and the stomachs were excised at 1, 6, and 24 hours later. Expression and localization of AM and AM-R mRNA were examined by competitive reverse transcription-polymerase chain reaction and in situ hybridization. AM protein expression was examined by Western blot analysis.


RESULTS
One hour after ethanol administration, AM mRNA expression in PHT gastric mucosa was significantly decreased by 81%, especially in the superficial mucosa, compared with the gastric mucosa in sham-operated rats. The significant decrease lasted for 24 hours. AM protein expression was significantly decreased by 43% compared with the sham-operated gastric mucosa. Although AM-R mRNA expression in both groups was significantly increased 1 hour after ethanol administration and lasted for 24 hours compared with baseline, there were no differences between the two groups.


CONCLUSIONS
The expression of AM in PHT gastric mucosa after ethanol-induced injury is significantly decreased compared with controls. This finding could explain one mechanism for the impaired angiogenesis after injury of PHT gastric mucosa.
Department of Surgery, Department of Veterans Affairs Medical Center, Long Beach, California 90822, USA.
M
M
Tomikawa
H
H
Wang
M K
MK
Jones
K
K
Sugimachi
I J
IJ
Sarfeh
A S
AS
Tarnawski
D053607:Adrenomedullin; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis* / Q000235:genetics; D000431:Ethanol / Q000008:administration & dosage; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006975:Hypertension, Portal / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D010455:Peptides; D012333:RNA, Messenger; D053607:Adrenomedullin; D000431:Ethanol; D015740:Calcitonin Gene-Related Peptide