Contrasting effects of vasodilators on oxygen tension and membrane potential of canine gastric surface epithelium.

Our purpose was to study the effects of three related vasoactive drugs on gastric epithelial oxygenation and metabolism. By means of an ultramicroelectrode technique, oxygen tension and transmembrane potential difference of surface epithelium were determined in an in vivo canine gastric chamber model. Intra-arterial papaverine (30 micrograms kg-1 min-1) caused a significant depression of epithelial PO2 and potential difference (PD), a transient inhibition of total gastric oxygen consumption, and a 70% increase in total gastric blood flow. Following cessation of the papaverine infusion, epithelial PO2 and PD continued to decline, whereas gastric blood flow and oxygen consumption return to baseline. Isoproterenol (0.0125 microgram kg-1 min-1), on the other hand, had no significant effect on epithelial PO2 and PD although it increased total gastric blood flow 33%. Dopamine (0.1 microgram kg-1 min-1) had no significant hemodynamic effects. To test the importance of papaverine-induced epithelial hypoxia, hydrochloric acid (160 mM) and sodium taurocholate (3 mM) were added to the epithelial bathing solution during intra-arterial infusion of either papaverine or isoproterenol. Necrosis and ulceration of the gastric mucosa were seen with the infusion of papaverine but not with the infusion of isoproterenol. Our results indicate that papaverine increases total gastric blood flow at the expense of nutrient blood flow to surface epithelium. We conclude that nutrient blood flow to surface epithelium is critical to the ability of the gastric mucosa to resist injury by luminal acid and bile. Furthermore, papaverine should not be used clinically to enhanced gastric blood flow because it is potentially injurious to the mucosa.