ROLE OF BRADYKININ IN THE HYPEREMIA FOLLOWING ACID CHALLENGE OF THE RAT GASTRIC-MUCOSA

1 This study examined whether the hyperaemia following acid challenge of the rat gastric mucosa involves bradykinin, a peptide formed in res ponse to tissue injury. 2 Gastric mucosal blood Bow in urethane-anaest hetized rats was assessed by the hydrogen gas clearance method. Infusi on of a bradykinin solution (10 mu M) into the gastric wall augmented gastric mucosal blood flow by a factor of 2.3, an effect that was prev ented by the bradykinin B-2 antagonist Hoe-140 (icatibant: 100 mu mol kg(-1), i.v.). 3 I.v. injection of bradykinin (20-60 nmol kg(-1)) caus ed a 2.3-3.5 fold increase in blood flow through the left gastric arte ry as measured by the ultrasonic transit time shift technique. The hyp eraemic effect of bradykinin in this gastric artery was also prevented by Hoe-140 (100 mu mol kg(-1), i.v.). 4 Gastric acid backdiffusion wa s evoked by perfusing the stomach with 15% ethanol, to break the gastr ic mucosal barrier, in the presence of luminal acid. Depending on the concentration of acid (0.05 and 0.15 M HCl), this procedure increased gastric mucosal blood flow by a factor of 1.6-2.8 and caused formation of gross damage in 1.5-3% of the glandular mucosa. Hoe-140 (100 mu mo l kg(-1), i.v.) failed to alter the moderate vasodilatation seen in th e presence of 0.05 M HCl but significantly (P<0.05) attenuated the mar ked hyperaemia and enhanced the gross mucosal damage observed in the p resence of 0.15 M HCl. 5 These data show that bradykinin is able to en hance gastric mucosal blood Bow via activation of B-2 receptors. It ap pears as if this kinin is formed during severe acid challenge of the r at gastric mucosa and participates in the hyperaemic reaction to gastr ic acid backdiffusion.