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1 Department of Pharmacology, University of Hawaii School of Medicine, Honolulu, Hawaii
The i.v. infusion of nicotine was found to protect anesthetized dogs against death produced by the infusion of KCl. The protection induced by nicotine appeared to be the result of the sympathetic discharge elicited by the drug as indicated by the observations that 1) the protection by nicotine is abolished by chlorisondamine, 2) the protection is also produced by epinephrine and 3) the protection by both nicotine and epinephrine is abolished by propranolol. Atropine pretreatment did not affect the protective action of nicotine and phenoxybenzamine did not affect that produced by epinephrine. Studies in anesthetized cats revealed that the protection against KCl toxicity could be obtained with agents having beta adrenergic stimulant properties (isoproterenol and epinephrine); phenylephrine, an alpha adrenergic stimulant, failed to protect. Plasma potassium data indicate that the protection is related to the ability of the beta stimulant drugs to attenuate the hyperkalemia produced by the KCl infusion. The latter as well as the protective action of the sympathomimetics against death produced by KCl infusion was abolished by propranolol. Acute nephrectomy did not affect the epinephrine induced protection or attenuation of the hyperkalemia produced by KCl infusion. These effects of epinephrine are thus subserved by beta adrenergic receptors and may involve the entry of potassium into cells.
Submitted on July 26, 1971