Effects of adrenergic agonists and antagonists in potassium intoxication
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1973
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University of Hawaii at Manoa
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Abstract
Studies were performed to assess the role of the sympathetic nervous system in regulating the metabolism of an administered load of potassium in anesthetized cats. A nonlethal intravenous infusion of KCl (10 mg/Kg/min for 10 minutes) produced effects indicative of a sympatho-adrenal discharge; these effects included an increase in heart rate, a rise in blood pressure and an increase in blood glucose. The increases in heart rate and blood pressure were abolished by acute adrenalectomy and by pretreatment with reserpine. Propranolol pretreatment antagonized the heart rate but not the blood pressure response associated' with the KCl infusion. Acute adrenalectomy as well as pretreatment with reserpine, propranolol and 1-(4'methylphenyl)-2- isopropylamino-propanol (H35/25) increased the susceptibility of the animals to KCl intoxication; thus, a significant number of fatalities occurred in these animals when they received a rate of KCl infusion (10 mg/Kg/min) which produced no deaths in intact, non-pretreated controls. The fatalities were correlated with higher plasma K+ values than in the controls. Butoxamine pretreatment did not significantly increase the susceptibility to KCl intoxication from a mortality standpoint but did significantly increase the hyperkalemic response to the KCl infusion. The above suggested that the sympatho-adrenal system has an important attenuating effect on the rise in plasma K+ produced by infusion of the ion. Chlorisondamine and bretylium pretreatment failed to increase the susceptibility of the animals to KCl intoxication. Evidence is presented which suggests that these latter two agents may not effectively antagonize the sympatho-adrenal discharge elicited by KCl infusion. The i.v. infusion of epinephrine completely protected animals against an infusion of KCl (12 mg/Kg/min for 10 minutes) which was lethal to most control animals. Plasma K+ data showed that the protection was related to an ability of epinephrine to attenuate the hyperkalemia produced by infusion of the ion. Similar effects on mortality and plasma K+ were produced by isoproterenol (a beta adrenergic stimulant) but not by phenylephrine (an alpha adrenergic stimulant). The epinephrine-induced protection against death due to KCl infusion as well as the plasma K+ lowering effect were abolished by propranolol and sotalol (beta blocking agents) but not by phenoxybenzamine (an alpha blocking agent). Acute nephrectomy or pancreatectomy did not affect the protective action of epinephrine. An infusion of glucose (which produced blood glucose levels higher than those in the epinephrine series) did not protect against KGI intoxication. The K+ content of skeletal and cardiac muscle in animals given an infusion of KCl was significantly greater in animals infused with epinephrine than in controls infused with saline. The foregoing suggests that epinephrine protected against KCl intoxication in these experiments by virtue of a direct beta stimulant action which promoted the entry of K+ into cells and thus prevented plasma K+ from reaching a lethal level. Studies were also performed to determine the "subtype" of beta receptor subserving the above effect on K+. Butoxamine and H35/25 were very effective in antagonizing the effects of epinephrine in potassium intoxication. Practolol, which blocked the cardiostimulant effect of epinephrine, did not block the protective effect or attenuation of hyperkalemia during KCI infusion by this catecholamine. Salbutamol and soterenol had effects similar to epinephrine, but l-isopropylamino-3-(2-thiazoloxy)2-propanol (ITP) failed to protect against KCl intoxication. The above spectrum of agonism and antagonism would be consistent with a beta-2 type of adrenergic receptor according to the Lands classification, although the adequacy of this classification in delineating the beta receptors found in different tissues has been questioned.
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Potassium--Toxicology, Potassium--Physiological effect, Sympathomimetic agents, Sympatholytic agents, Cats--Physiology
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Theses for the degree of Doctor of Philosophy (University of Hawaii at Manoa). Biomedical Sciences (Pharmacology); no.539
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