[Evaluation of the mechanism of endothelin-induced rat gastric mucosal lesion formation].
There are several reports on the gastric mucotoxic effect of endothelin (ET). The mechanism of this effect, however, remains largely unknown. To evaluate this, we assessed the gastric injury and changes in gastric mucosal blood flow induced by ET using ONO-1078, a sulfide peptide leukotriene (LT) antagonist, CV-3988, a platelet-activating factor (PAF) antagonist, and diltiazem, a Ca2+ channel blocker. In fasted and anesthetized rats, 2 nmol/kg of ET was infused for 30 min into splenic artery to deliver the drug as much as selectively to the stomach. Ninety minutes after beginning the drug infusion rats were killed and gastric mucosal damage in the removed stomachs was assessed. Gastric mucosal blood flow (GMBF) was measured for 90 min with a 30 min-interval by the laser Doppler flowmetry method. ET induced severe gastric mucosal damage, which was characterized by congestion of mucosal capillary and accompanied by significant reduction of GMBF, as compared with control. However, these mucotoxic effect of ET was significantly inhibited by 20 mg/kg of ONO-1078 given i. g. 60 min before ET infusion and i. v. administration of 10 mg/kg of CV-3988 and 1 mg/kg of diltiazem 30 min prior to ET. From these results, we conclude that PAF, LT and Ca2+ may play important pathogenetic roles as chemical mediators in the mechanism of the formation of ET-induced gastric mucosal lesions.
Katoh
N
N
Department of Internal Medicine, Nagoya-shi Koseiin Hospital.
Itoh
M
M
Yokoyama
Y
Y
Joh
T
T
D000818:Animals; D002118:Calcium / Q000502:physiology; D002867:Chromones / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D016232:Endothelins / Q000633:toxicity*; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D015289:Leukotrienes / Q000502:physiology; D008297:Male; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013189:SRS-A / Q000037:antagonists & inhibitors
D002867:Chromones; D016232:Endothelins; D015289:Leukotrienes; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D013189:SRS-A; C037913:CV 3988; D004110:Diltiazem; D002118:Calcium; C047681:pranlukast