title: Differences in action of topical and systemic cysteamine on gastric blood flow, gastric acid secretion and gastric ulceration in the rat.
abstract: The effect of cysteamine on gastric blood flow and on the indomethacin-induced gastric mucosal damage was studied. In anesthetized rats, cysteamine (280 mg/kg) given subcutaneously (s.c.) decreased gastric blood flow measured by the laser Doppler flowmetry technique. In contrast, cysteamine (1-60 mg/ml) applied topically to the serosal surface of the stomach evoked a concentration-dependent and long-lasting increase in gastric blood flow. At 60 mg/ml, cysteamine increased blood flow by 166.8 +/- 26.1% of predrug control value. Pretreatment with indomethacin (20 mg/kg, s.c.), intravenous (i.v.) atropine (1 mg/kg), propranolol (1 mg/kg, i.v.), combined H1 and H2-blockade or bilateral cervical vagotomy alone or combined with i.v. guanethidine (8 mg/kg), or pretreatment with the capsaicin analogue resiniferatoxin did not reduce the vasodilator response to cysteamine. The vasodilator response to topical capsaicin, was not reduced after s.c. cysteamine (280 mg/kg) pretreatment. In conscious pylonus-ligated rats, s.c. cysteamine (100 or 280 mg/kg) given simultaneously with indomethacin inhibited gastric acid output but had variable effects on the indomethacin-induced gastric mucosal damage. Cysteamine (100 or 280 mg/kg) administered s.c. 4 h prior to indomethacin enhanced gastric injury by s.c. indomethacin, but did not prevent the gastroprotective action of capsaicin. In contrast, orally administered cysteamine (60 mg/ml) reduced gastric injury induced by s.c. indomethacin plus intragastric HCl. These data provide the first evidence for the effect of cysteamine on gastric microcirculation in the rat and suggest a direct vasodilator effect for topical cysteamine. The microvascular effects of cysteamine are largely responsible for the different effects of this agent on experimental gastric injury.
authors.affiliation: First Department of Medicine, Medical University of Pécs, Hungary.
authors.forename: O
authors.initials: O
authors.lastname: Abdel-Salam
authors.forename: J
authors.initials: J
authors.lastname: Szolcsányi
authors.forename: G
authors.initials: G
authors.lastname: Mózsik
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D003543:Cysteamine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D006727:Hormone Antagonists / Q000378:metabolism; D007279:Injections, Subcutaneous; D007441:Intubation, Gastrointestinal; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013004:Somatostatin / Q000378:metabolism; D013270:Stomach / Q000098:blood supply* / Q000187:drug effects; D013276:Stomach Ulcer / Q000473:pathology*
chemical_list: D006727:Hormone Antagonists; D013004:Somatostatin; D003543:Cysteamine; D002211:Capsaicin