Role of bradykinin in the hyperaemia 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 response to tissue injury. 2. Gastric mucosal blood flow in urethane-anaesthetized rats was assessed by the hydrogen gas clearance method. Infusion of a bradykinin solution (10 microM) into the gastric wall augmented gastric mucosal blood flow by a factor of 2.3, an effect that was prevented by the bradykinin B2 antagonist Hoe-140 (icatibant; 100 mumol kg-1, i.v.). 3. I.V. injection of bradykinin (20-60 nmol kg-1) caused a 2.3-3.5 fold increase in blood flow through the left gastric artery as measured by the ultrasonic transit time shift technique. The hyperaemic effect of bradykinin in this gastric artery was also prevented by Hoe-140 (100 mumol kg-1, i.v.). 4. Gastric acid back diffusion was evoked by perfusing the stomach with 15% ethanol, to break the gastric 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 mumol kg-1, i.v.) failed to alter the moderate vasodilatation seen in the presence of 0.05 M HCl but significantly (P < 0.05) attenuated the marked hyperaemia and enhanced the gross mucosal damage observed in the presence of 0.15 M HCl. 5. These data show that bradykinin is able to enhance gastric mucosal blood flow via activation of B2 receptors. It appears as if this kinin is formed during severe acid challenge of the rat gastric mucosa and participates in the hyperaemic reaction to gastric acid back diffusion.
Pethö
G
G
Department of Experimental and Clinical Pharmacology, University of Graz, Austria.
Jocic
M
M
Holzer
P
P
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply*; D006940:Hyperemia / Q000209:etiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects
C065679:icatibant; D001920:Bradykinin