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 stimulated by messengers generated in the injured gastric mucosa. This study was undertaken to analyse the gastric factors that are responsible for the femoral vasoconstrictor response. 2. Gastric mucosal barrier disruption in the presence of luminal acid was induced by perfusing the stomach of urethane-anaesthetized rats with ethanol (15 %) in 0.01-0.15 M HCl. Blood flow in the left gastric and right femoral artery was estimated by the ultrasonic transit time shift technique. 3. Gastric perfusion of ethanol in HCl caused loss of H+ ions from the gastric lumen, decreased the HCO3- concentration in hepatic portal vein blood, induced macroscopic histological damage to the gastric mucosa, dilated the left gastric artery and constricted the femoral artery. These responses were related to the HCl concentration in the ethanol-containing perfusion medium. 4. The femoral vasoconstriction was also seen when, instead of ethanol, taurocholate (20 mM) was used to disrupt the gastric mucosal barrier in the presence of 0.15 M HCl. 5. The femoral vasoconstriction evoked by gastric perfusion of ethanol in HCl was left unaltered by pharmacological blockade of gastrin and histamine receptors. In contrast, the 5-hydroxytryptamine 5-HT1/2 receptor antagonist methiothepin, but not the 5-HT2A receptor antagonist ketanserin or the 5-HT3 receptor antagonist granisetron, inhibited the ability of both 5-hydroxytryptamine and gastric acid back-diffusion to constrict the femoral artery. 6. Gastric acid back-diffusion caused release of 5-hydroxytryptamine into the gastric lumen, which was related to the HCl concentration in the ethanol-containing perfusion medium. 7. These data show that femoral vasoconstriction evoked by gastric mucosal barrier disruption depends on back-diffusion of acid into the mucosa. The acid-induced damage results in release of 5-hydroxytryptamine from the gastric mucosa, and the pathway leading to constriction of the femoral artery involves 5-hydroxytryptamine acting via 5-HT1/2 receptors as a messenger molecule.
Wachter
C H
CH
Department of Experimental and Clinical Pharmacology, University of Graz, A-8010 Graz, Austria.
Heinemann
A
A
Donnerer
J
J
Pabst
M A
MA
Holzer
P
P
D000818:Animals; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology*; D005744:Gastric Acid / Q000502:physiology; D005753:Gastric Mucosa / Q000098:blood supply* / Q000473:pathology / Q000502:physiology*; D017829:Granisetron / Q000494:pharmacology; D006851:Hydrochloric Acid / Q000494:pharmacology*; D007650:Ketanserin / Q000494:pharmacology; D008719:Methiothepin / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D012039:Regional Blood Flow; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013656:Taurocholic Acid / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D000431:Ethanol; D017829:Granisetron; D006851:Hydrochloric Acid; D007650:Ketanserin; D008719:Methiothepin; D011985:Receptors, Serotonin; D012701:Serotonin; D012702:Serotonin Antagonists; D013656:Taurocholic Acid