Summary
The effects of intravenous norepinephrine infusion (0.5 mg/kg in two hours) in conscious dogs can be classified according to the influence of pretreatment with phenoxybenzamine (2 or 5 mg/kg intravenously one hour before norepinephrine) or isopropylmethoxamine (BW 61-43) (8 mg/kg intravenously 20 to 30 minutes before infusion). Effects blocked or reduced by phenoxybenzamine, but not by BW 61-43, include the rise in arterial pressure, electrocardiographic changes, accumulation of pericardial fluid rich in lactic dehydrogenase, the rise in hematocrit, presence of inclusion bodies in liver cells, and necrosis of the adrenal cortex. Effects blocked by BW 61-43, but not by phenoxybenzamine, include the rises in plasma FFA and glucose and the accumulation of triglycerides in liver. Both phenoxybenzamine and BW 61-43 block, at least partially, the accumulation of triglycerides in heart. Neither phenoxybenzamine nor BW 61-43 prevents the norepinephrine-induced depletion of glycogen in liver.
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Barnett, H.: Electrophoretic separation of lactate dehydrogenase isoenzymes on cellulose acetate. Biochem. J. 84, 83 P (1962).
Bloom, F.: Pathology of the Dog and Cat. The Genitourinary System with Clinical Considerations pp. 8–9. Evanston, Illinois: American Veterinary Publications, Inc. 1954.
Brodie, B. B., and R. P. Maickel: Role of the sympathetic nervous system in drug-induced fatty liver. Ann. N. Y. Acad. Sci. 104, 1049–1058 (1963).
Burns, J. J., and K. I. Colville: Potent effect of the adrenergic blocking agent, BW 61-43, in lowering fasting levels of free fatty acids in dog and man. The Pharmacologist 4, 178 (1962).
Butler, W. M., jr., H. M. Maling, M. G. Horning, and B. B. Brodie: The direct determination of liver triglycerides. J. Lipid Res. 2, 95–96 (1961).
Dole, V. P.: A relation between non-esterified fatty acids in plasma and the metabolism of glucose. J. clin. Invest. 35, 150–154 (1956).
Drummond, W. B.: The histological changes produced by the injection of adrenalin chloride. J. Physiol. 31, 81–91 (1904).
Eaton, P., and D. Steinberg: Effects of medium fatty acid concentration, epinephrine, and glucose on palmitate-1-C14 oxidation and incorporation into neutral lipids by skeletal muscle in vitro. J. Lipid Res. 2, 376–382 (1961).
Ellis, S.: The metabolic effects of epinephrine and related amines. Pharmacol. Rev. 8, 485–565 (1956).
Feigelson, E. B., W. W. Pfaff, A. Karmen, and D. Steinberg: The role of plasma free fatty acids in development of fatty liver. J. clin. Invest. 40, 2171–2179 (1961).
Gourzis, J. T., N. Roque, and M. Nickerson: Chemical structure and antishock activity among compounds related to phenoxybenzamine (Dibenzyline). J. Pharmacol. exp. Ther. 141, 314–320 (1963).
Handel, E. van, and D. B. Zilversmit: Micromethod for the direct determination of serum triglycerides. J. Lab. clin. Med. 50, 152–157 (1957).
Havel, R. J., and A. Goldfien: The role of the sympathetic nervous system in the metabolism of free fatty acids. J. Lipid Res. 1, 102–108 (1959).
Highman, B., H. M. Maling, and E. C. Thompson: Serum transaminase and alkaline phosphatase levels after large doses of norepinephrine and epinephrine in dogs. Amer. J. Physiol. 196, 436–440 (1959).
Horning, M. G., M. J. Earle, and H. M. Maling: Changes in fatty acid composition of liver lipids induced by carbon tetrachloride and ethionine. Biochim. biophys. Acta (Amst.) 56, 175–177 (1962).
—, and H. M. Maling: Biochemical processes involved in the synthesis, accumulation and release of triglycerides in the liver. In: Proceedings of the First International Pharmacological Meeting, Symposium on Effects of Drugs on Synthesis and Mobilization of Lipids. Vol. 2, p. 13–27. Oxford: Pergamon Press 1963.
—, and B. B. Brodie: Depot fat as source of increased liver triglycerides after ethanol. Biochem. biophys. Res. Commun. 3, 635–640 (1960).
Kohn, J.: Cellulose acetate electrophoresis and immuno-diffusion techniques. In: Chromatographic and Electrophoretic Techniques. Vol. 2, p. 56–90 New York: Interscience 1960.
Lillie, R. D.: Histopathologic Technique and Practical Histochemistry, p. 55 and 120–128. New York: The Blakiston Company 1954.
Maickel, R. P., and B. B. Brodie: Interaction of drugs with the pituitary-adrenocortical system in the production of the fatty liver. Ann. N. Y. Acad. Sci. 104, 1059–1064 (1963).
Maling, H. M., A. Frank, and M. G. Horning: Effect of carbon tetrachloride in hepatic synthesis and release of triglycerides. Biochim. biophys. Acta (Amst.) 64, 540–545 (1962).
— and B. Highman: Exaggerated ventricular arrhythmias and myocardial fatty changes after large doses of norepinephrine and epinephrine in unanesthetized dogs. Amer. J. Physiol. 194, 590–596 (1958).
—, and E.C. Thompson: Some similar effects after large doses of catecholamines and myocardial infarction in dogs. Amer. J. Cardiol. 5, 628–633 (1960).
—, and M. G. Horning: Alterations in hepatic lipid biosynthetic pathways after ethanol, ethionine, and carbon tetrachloride. In: Advances in Enzyme Regulation. Vol. 1, p. 247–257. Oxford: Pergamon Press 1963.
Maurer, F. W., M. F. Warren, and C. K. Drinker: The composition of mammalian pericardial and peritoneal fluids. Amer. J. Physiol. 129, 635–644 (1940).
Mayer, S., N. C. Moran, and J. Fain: The effect of adrenergic blocking agents on some metabolic actions of catecholamines. J. Pharmacol. exp. Ther. 134, 18–27 (1961).
Moran, N. C., and M. E. Perkins: An evaluation of adrenergic blockade of the mammalian heart. J. Pharmacol. exp. Ther. 133, 192–201 (1961).
Nickerson, M., and C. C. Chan: Blockade of responses of isolated myocardium to epinephrine. J. Pharmacol. exp. Ther. 133, 186–191 (1961).
Pilkington, T. R. E., and R. D. Lowe: Effect of adrenergic blockade on glucose and fatty-acid mobilization in man. Lancet 18, 316–317 (1962).
Rebouças, G., and K. J. Isselbacher: Studies on the pathogenesis of the ethanol-induced fatty liver. 1. Synthesis and oxidation of fatty acids by the liver. J. clin. Invest. 40, 1355–1362 (1961).
Recknagel, R. O., B. Lombardi, and M. C. Schotz: A new insight into pathogenesis of carbon tetrachloride fat infiltration. Proc. Soc. exp. Biol. (N.Y.) 104, 608–610 (1960).
Rosenthale, M. E., and J. R. DiPalma: Acute tolerance to norepinephrine in dogs. J. Pharmacol. exp. Ther. 136, 336–343 (1962).
Salvador, R. A., K. I. Colville, L. A. Lindsay, and J. J. Burns: Ability of the N-isopropyl derivative of methoxamine (B. W. 61-43) to block the metabolic effects of epinephrine. Fed. Proc. 22, 508 (1963).
Schotz, M. C., and I. H. Page: Effect of adrenergic blocking agents on the release of free fatty acids from rat adipose tissue. J. Lipid. Res. 1, 466–468 (1960).
Shmerling, M. D.: Special features of myocardial venous system. Fed. Proc. 22, T773-T777 (1963). Translated from Arkhiv Anatomii, Gistologii i Embriologii 42, 14 (1962).
Trout, D. L., E. H. Estes jr., and S. J. Friedberg: Titration of free fatty acids of plasma: a study of current methods and a new modification. J. Lipid Res. 1, 199–202 (1960).
Waters, L. I., and G. I. de Suto-Nagy: Circulatory factors in the pathogenesis of experimental arteriolar necrosis. Yale J. Biol. Med. 22, 751–766 (1950).
Zhdanov, D. A.: General Anatomy and Physiology of the Lymphatic System. Moscow (1952). Cited by Shmerling, M. D. Fed. Proc. 22, T773–T777 (1963).
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This paper is dedicated to Professor Otto Krayer on his 65th birthday.
A preliminary report was presented at the Fall Meeting of the American Society for Pharmacology and Experimental Therapeutics, August 14, 1963, San Francisco, California. An abstract was published in The Pharmacologist 5, 257 (1963).
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Maling, H.M., Williams, M.A., Highman, B. et al. The influence of phenoxybenzamine and isopropylmethoxamine (BW 61-43) on some cardiovascular, metabolic, and histopathologic effects of norepinephrine infusions in dogs. Naunyn - Schmiedebergs Arch 248, 54–72 (1964). https://doi.org/10.1007/BF00247059
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DOI: https://doi.org/10.1007/BF00247059