Impaired vasodilatory responses in the gastric microcirculation of anesthetized rats with secondary biliary cirrhosis

Gastroenterology. 1995 Apr;108(4):1183-91. doi: 10.1016/0016-5085(95)90218-x.


Background/aims: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Anesthesia
  • Animals
  • Calcitonin Gene-Related Peptide / metabolism
  • Capsaicin / pharmacology
  • Cyclic GMP / analogs & derivatives
  • Cyclic GMP / pharmacology
  • Disease Models, Animal
  • Hyperemia / etiology
  • Hypertension, Portal / complications
  • Laser-Doppler Flowmetry
  • Liver Cirrhosis, Biliary / etiology
  • Liver Cirrhosis, Biliary / metabolism
  • Liver Cirrhosis, Biliary / physiopathology*
  • Male
  • Microcirculation / drug effects
  • Microcirculation / physiopathology
  • Misoprostol / pharmacology
  • Neurons, Afferent / physiology
  • Nitroprusside / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Stomach / blood supply*
  • Stomach / innervation
  • Vasodilation* / drug effects


  • Misoprostol
  • Nitroprusside
  • 8-Bromo Cyclic Adenosine Monophosphate
  • 8-bromocyclic GMP
  • Cyclic GMP
  • Calcitonin Gene-Related Peptide
  • Capsaicin