MEDIATION BY 5-HYDROXYTRYPTAMINE OF THE FEMORAL VASOCONSTRICTION INDUCED BY ACID CHALLENGE OF THE RAT GASTRIC-MUCOSA

1. Gastric mucosal barrier disruption in the presence of luminal acid causes femoral vasoconstriction via a pathway that appears to be stimu lated by messengers generated in the injured gastric mucosa. This stud y was undertaken to analyse the gastric factors that are responsible f or the femoral vasoconstrictor response. 2. Gastric mucosal barrier di sruption in the presence of luminal acid was induced by perfusing the stomach of urethane-anaesthetized rats with ethanol (1.5%) in 0.01-0.1 5 M HCl. Blood flow in the left gastric and right femoral artery was e stimated by the ultrasonic transit time shift technique. 3. Gastric pe rfusion of ethanol in HCl caused loss of H+ ions from the gastric lume n, decreased the HCO3- concentration in hepatic portal vein blood, ind uced macroscopic histological damage to the gastric mucosa, dilated th e left gastric artery and constricted the femoral artery. These respon ses were related to the HCl concentration in the ethanol-containing pe rfusion medium. 4. The femoral vasoconstriction was also seen when, in stead of ethanol, taurocholate (20 mM) was used to disrupt the gastric mucosal barrier in the presence of 0.15 M HCl. 5. The femoral vasocon striction evoked by gastric perfusion of ethanol in HCl was left unalt ered by pharmacological blockade of gastrin and histamine receptors. I n contrast, the 5-hydroxytryptamine 5-HT1/2 receptor antagonist methio thepin, but not the 5-HT2A receptor antagonist ketanserin or the 5-HT3 A receptor antagonist granisetron, inhibited the ability of both 5-hyd roxytryptamine and gastric acid back-diffusion to constrict the femora l artery. 6. Gastric acid back-diffusion caused release of 5-hydroxytr yptamine into the gastric lumen, which was related to the HCl concentr ation in the ethanol-containing perfusion medium. 7. These data show t hat femoral vasoconstriction evoked by gastric mucosal barrier disrupt ion depends on back-diffusion of acid into the mucosa. The acid-induce d damage results in release of 5-hydroxytryptamine from the gastric mu cosa, and the pathway leading to constriction of the femoral artery in volves 5-hydroxytryptamine acting via 5-HT1/2 receptors as a messenger molecule.