Mediators of bile acid-induced alterations in gastric mucosal blood flow

The topical application of acidified (pH 1.2) bile acids to acid-peptic-secreting gastric mucosa increases mucosal blood flow, an important protective event because, when it is blunted, gross mucosal injury occurs. The mediators of this response are unknown. The current study examined the potential roles of luminal pH, luminal bile acid concentration, and, indirectly, endogenous prostaglandin generation in groups of dogs prepared with ex vivo chambered wedges of proximal gastric wall. Parameters evaluated included H+ fluxes, mucosal blood flow using radiolabeled microspheres, and the severity of gross mucosal injury induced at high and low intraluminal pH (7 and 1.2), at differing concentrations of bile acid (0, 2.5, 5.0 mM), in the presence of indomethacin pretreatment with or without concomitant close intra-arterial infusion of prostacyclin. The results indicate that topical bile acids increase mucosal blood flow in proportion to their capacity to induce H+ loss. This response is blunted (but not ablated) by indomethacin, resulting in gross mucosal injury, effects that are reversed by prostacyclin infusion. Thus, in large part, endogenous prostaglandins are its likely mediators.