Differences in action of topical and systemic cysteamine on gastric blood flow, gastric acid secretion and gastric ulceration in the rat.
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.
Abdel-Salam
O
O
First Department of Medicine, Medical University of Pécs, Hungary.
Szolcsányi
J
J
Mózsik
G
G
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*
D006727:Hormone Antagonists; D013004:Somatostatin; D003543:Cysteamine; D002211:Capsaicin