Vascular injury in acute gastric mucosal damage. Mediatory role of leukotrienes.
Recent investigations indicate that microvascular injury, leading to increased vascular permeability and capillary stasis, precede the development of chemically induced hemorrhagic mucosal lesions in the stomach. The vascular damage is more amenable to protection by prostaglandins and sulfhydryls than the diffuse surface mucosal cell injury. The vascular and mucosal lesions may be the result of direct toxicity of damaging agents (eg, ethanol, HCl, NaOH) and the release of vasoactive amines and leukotrienes. We review here our recent studies performed in rats indicating that intraarterial infusion of LTC4 or LTD4 in the stomach caused vascular injury as revealed by monastral blue. Infusion of leukotrienes alone caused no hemorrhagic mucosal lesions but aggravated the damage caused by 25, 50, or 100% ethanol and 0.2 N HCl given intragastrically. The ethanol-induced mucosal lesions were slightly diminished by the lipoxygenase inhibitor L-651,392 and markedly decreased by eicosapentaenoic acid, which competes with arachiconic acid as a substrate for 5-lipoxygenase. These results are discussed and correlated with biochemical results from other laboratories demonstrating increased levels of leukotrienes in the gastric mucosa after administration of ethanol and decreased release following pretreatment with prostaglandins or sulfhydryl-related agents. New data thus support a mediatory role for leukotrienes in the pathogenesis of vascular injury and mucosal lesions in the stomach.
Pihan
G
G
Department of Pathology, Brigham & Women's Hospital, Boston, Massachusetts 02115.
Rogers
C
C
Szabo
S
S
D000818:Animals; D002199:Capillary Permeability; D000431:Ethanol / Q000633:toxicity; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects; D006471:Gastrointestinal Hemorrhage / Q000209:etiology; D006851:Hydrochloric Acid / Q000633:toxicity; D016859:Lipoxygenase Inhibitors; D010640:Phenothiazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000502:physiology*; D013276:Stomach Ulcer / Q000209:etiology*
D016859:Lipoxygenase Inhibitors; D010640:Phenothiazines; D013189:SRS-A; D000431:Ethanol; C053726:4-bromo-2,7-dimethoxy-3H-phenothiazin-3-one; D006851:Hydrochloric Acid