Impaired vasodilatory responses in the gastric microcirculation of anesthetized rats with secondary biliary cirrhosis.
OBJECTIVE
The increased susceptibility of the stomach to injury observed in portal hypertension may be related to a defect in the hyperemic response to luminal irritants. The aim of this study was to evaluate the components that mediate this hyperemic response in a rat model of cirrhosis and portal hypertensive gastropathy.


METHODS
Cirrhosis was induced by bile duct ligation, whereas controls underwent sham operation. Gastric blood flow responses to topical application of acid, capsaicin, nitrovasodilators, misoprostol, 8-bromo-cyclic guanosine monophosphate, and 8-bromo-cyclic adenosine monophosphate were measured by laser Doppler flowmetry using an ex vivo gastric chamber preparation. Calcitonin gene-related peptide immunoreactivity was used as an index of the anatomic integrity of the sensory afferent neurons of the stomach.


RESULTS
Blood flow responses to acid, capsaicin, nitrovasodilators, and 8-bromo-cyclic guanosine monophosphate were significantly depressed in cirrhotic rats, whereas they were augmented after topical application of misoprostol and 8-bromo-cyclic adenosine monophosphate. Calcitonin gene-related peptide immunoreactivity was similar in the stomachs of cirrhotic and control rats.


CONCLUSIONS
Gastric vasodilation after stimulation of sensory afferent neurons is impaired in cirrhotic rats despite the normal anatomic distribution of these nerves. This effect seemed to be related to a depressed response of the gastric microcirculation to cyclic guanosine monophosphate-dependent vasodilators. This alteration may contribute to the increased susceptibility to gastric ulceration in cirrhotics.
Ferraz
J G
JG
Gastrointestinal Research Group, Faculty of Medicine, University of Calgary, Alberta, Canada.
McKnight
W
W
Sharkey
K A
KA
Wallace
J L
JL
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D006940:Hyperemia / Q000209:etiology; D006975:Hypertension, Portal / Q000150:complications; D017078:Laser-Doppler Flowmetry; D008105:Liver Cirrhosis, Biliary / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology; D016595:Misoprostol / Q000494:pharmacology; D009475:Neurons, Afferent / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000098:blood supply* / Q000294:innervation; D014664:Vasodilation / Q000187:drug effects
D016595:Misoprostol; D009599:Nitroprusside; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016276:8-bromocyclic GMP; D006152:Cyclic GMP; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin