The Inhibition of Ischemic Lesions of the Rat Gastric Mucosa by a Novel Serotonin- Antagonist: a Light and Electron Microscopic Study

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Abstract
Two methods that provoke severe lesions in the rat gastric wall were used to study the pathologic action of serotonin. In a first group of rats 1 mg/kg of compound 48/80 was injected IV. The lethal shock that follows within about 30 minutes was prevented by subcutaneous administration of a H1- antagonist. This treatment did not suppress the gastric gland activity, in particular the gastric secretion, and resulted in time-related lesions situated in the gastric corpus and to a lesser extent in the antrum. In a second group of rats similar lesions were induced by slow infusion of 30 μg/kg/min serotonin into the femoral vein. The earliest observed light microscopic events concerned mucosal vessel appearance. Most of the vessels were heavily dilated and engorged with blood cells. The most important ultrastructural changes were seen in the various epithelial cells. These were characterized by an early disappearance of intramitochondrial granular deposits. In a later stage progressive necrosis of the epithelial cells was observed. Lesions evolving from focal edematous erosions into deep necrotic and hemorrhagic wounds were found throughout the whole gastric wall. These final severe lesions were attributed to a local vascular congestion which led to cellular ischemia and a consequent energy deficiency of the mucosal cells. When rats were orally pretreated with the novel serotonin-antagonist R 41 468 at a dose of 0.63 mg/kg, the light and electron microscopic picture was almost completely comparable to that of unchallenged animals. This indi cates that R 41 468 is a potent antagonist of peripheral venoconstriction induced by infused exogenous serotonin as well as by released endogenous serotonin.