Hepatic necrosis induced by norepinephrine in rabbits.
Extensive hepatic necrosis was produced in rabbits 48 hr following infusion of a cardiopathogenic dose of norepinephrine (NE, 2 micrograms/kg/min for 90 min). Livers had necrotic areas of varying sizes and gross appearances. Histologically, the lesions were areas of varying sizes and gross appearances. Histologically, the lesions were areas of lytic-coagulative necrosis with massive mineralization by calcium. In addition, the serum glutamate-pyruvate transaminase (GPT) was significantly elevated (P less than 0.001). Pretreatment with the alpha 1-adrenoceptor blocker prazosin (200 micrograms/kg) 15 min prior to the standard NE infusion prevented both liver necrosis and serum GPT elevation. It is concluded that large doses of NE produce tissue injury in the liver. This may be the result of excessive activation of the alpha 1-adrenoceptor system, which leads to hepatic ischemia and necrosis.
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002118:Calcium / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology; D009336:Necrosis; D009638:Norepinephrine / Q000633:toxicity*; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000502:physiology
D011942:Receptors, Adrenergic, alpha; D000410:Alanine Transaminase; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin