Clinical Investigation

Kidney International (1990) 37, 793–798; doi:10.1038/ki.1990.47

Adrenergic modulation of potassium metabolism in uremia

Pietro Castellino, Margaret J Bia and Ralph A DeFronzo

Divisions of Nephrology and Diabetes, University of Texas Health Science Center, San Antonio, Texas and Division of Nephrology, Yale University School of Medicine, New Haven, Connecticut, USA; and Istituto di Medicina Interna e Nefrologia, Universita di Napoli, Italy

Correspondence: Ralph A DeFronzo MD, Diabetes Division, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78284, USA.

Received 27 October 1988; Revised 25 August 1989; Accepted 1 September 1989.

Top

Abstract

Adrenergic modulation of potassium metabolism in uremia. The effect of chronic beta adrenergic blockade on potassium homeostasis during moderate intensity exercise (40% of VO2 max) was examined in seven end-stage renal patients who were being maintained on chronic dialysis treatment. Subjects participated in three study protocols: 1) exercise alone, 2) exercise plus propranolol (a nonselective beta-1, beta-2 antagonist), and 3) exercise plus metoprolol (a specific beta-1 antagonist). The basal potassium concentration was similar in all three studies and averaged 4.95 plusminus 0.12 mEq/liter. During Study 1 (exercise alone), plasma potassium rose by 0.26 plusminus 0.09 mEq/liter. During exercise with propranolol, plasma K concentration rose significantly higher (Delta plasma K = 0.44 plusminus 0.26 mEq/liter; P < 0.05 vs. exercise alone). In contrast, the rise in plasma K during exercise with metoprolol (Delta plasma K = 0.20 plusminus 0.08 mEq/liter) was similar to that observed with exercise alone. Differences in potassium homeostasis between metoprolol and propranolol could not be explained by differences in hemodynamic parameters, levels of potassium regulatory hormones, or acid base status. Thus, the higher rise in potassium concentration during exercise with propranolol could only be explained by adrenergic blockade at the beta-2 receptor site. These results support the concept that adrenergic control of extrarenal potassium homeostasis in dialysis patients is mediated at the beta-2 receptor. Since a deterioration in potassium homeostasis during exercise is observed with beta-2, but not beta-1 blockade, selective beta-1 adrenergic blocking agents may be safer in dialysis patients.

Top

References

  1. DeFronzo RA, Bia M: Extrarenal potassium homeostasis, in The Kidney: Physiology and Pathophysiology, edited by Seldin DW, Giebisch G, New York, Raven Press, 1985, pp. 1179–1206
  2. DeFronzo RA, Felig P, Ferrannini E, Wharen J: Effect of graded doses of insulin on splanchnic and peripheral potassium metabolism in man. Am J Physiol 238:E421–E427, 1980
  3. DeFronzo RA, Sherwin RS, Dillingham M, Hendler R, Tamborlane WV, Felig P: Influence of basal insulin and glucagon secretion on potassium and sodium metabolism. J Clin Invest 61:472–179, 1978
  4. Hiatt N, Yamakawa T, Davidson MB: Necessity for insulin in transfer of excess infused K to intracellular fluid. Metabolism 23:43–49, 1974 | PubMed |
  5. Rosa RM, Silva P, Young JB, Landsberg L, Brown RS, Rowe JW, Epstein FH: Adrenergic modulation of extrarenal potassium disposal. N Engl J Med 302:431–434, 1980
  6. DeFronzo RA, Bia M, Birkhead G: Epinephrine and potassium homeostasis. Kidney Int 20:83–91, 1981
  7. Brown MJ, Brown DC, Murphy MG: Hypokalemia from beta2-receptor stimulation by circulating epinephrine. N Engl J Med 309:1414–1419, 1983
  8. Lockwood RH, Lum BKB: Effects of adrenergic agonists and antagonists on potassium metabolism. J Pharmacol Exp Ther 189:119–129, 1974
  9. Bia MJ, Lu D, Tyler K, DeFronzo RA: Beta adrenergic control of extrarenal potassium disposal. A beta-2 mediated phemonemon. Nephron 43:117–122, 1986
  10. Castellino P, Simonson DC, DeFronzo RA: Adrenergic modulation of potassium metabolism during exercise in normal and diabetic humans. Am J Physiol 252:E68–E76, 1987
  11. Arrizabalaga P, Montoliu J, Martinez Vea A, Andreu L, Lopez Pedret J, Revert L: Increase in serum potassium caused by beta-2 adrenergic blockade in terminal renal failure: Absence of mediation by insulin or aldosterone. Proc Eur Dial Transplant Assoc 20:572–576, 1983 | PubMed | ISI | ChemPort |
  12. Rosselin G, Assan R, Yalow RS, Berson SA: Separation of antibody-bound and unbound peptide hormones labelled with iodine-131 by talcum powder and precipitated silica. Nature 212:355–357, 1966 | Article |
  13. Aguilar-Parada E, Eisentraut AM, Unger RH: Pancreatic glucagon secretion in normal and diabetic subjects. Am J Med Sci 257:415–419, 1969
  14. Buhler F, Sealy JE, Laragh JH: Hypertension Manual: Mechanisms, Methods, Management, edited by Laragh J, New York, York Medical Books, 1974, pp. 655–669
  15. Castellino P, Bia MJ, DeFronzo RA: Metabolic response to exercise in dialysis patients. Kidney Int 32:877–883, 1987
  16. Smith JD, Bia MJ, DeFronzo RA: Clinical disorders of potassium metabolism, in Fluid, Electrolyte, and Acid-Base Disorders, edited by Arieff AI, DeFronzo RA, New York, Churchill Livingstone, 1985, pp. 413–510
  17. Degoulet P, Legrain M, Reach I, Aime F, Devries C, Rojas P, Jacobs C: Mortality risk factors in patients treated by chronic hemodialysis: Report of the Diaphane collaborative study. Nephron 31:103–110, 1982 | PubMed | ISI | ChemPort |
  18. Clausen T, Flatman JA: Beta 2 adrenoceptors mediate the stimulating effect of adrenaline on active electrogenic Na-K transport in rat soleus muscle. Br J Pharmacol 68:749–755, 1980 | PubMed | ChemPort |
  19. Allan M, Dunlay R, Copkney C: Nebulized albuterol for acute hyperkalemia in patients on hemodialysis. Ann Int Med 110:426–429, 1989
  20. Yang WC, Huang TP, Ho LT, Chung HM, Chan YL, Battle DC: Propranolol-induced hyperkalemia in non-diabetic uremic patients. (abstract) Kidney Int 27:156A, 1985
  21. Houben H, Thieu T, Van't Laar A: Effect of low-dose epinephrine infusion on hemodynamics after selective and nonselective beta-blockade in hypertension. Clin Pharm Ther 31:685–690, 1982
  22. Westaby D, Melia WM, Macdougall BRD, Hegarty JE, Gimson AE, Williams R: B1 selective adrenoreceptor blockade for the long term management of variceal bleeding. A prospective 26. randomized trail to compare oral metoprolol with injection sclerotherapy in cirrhosis. Gut 26:421–425, 1985
  23. Kullmer T, Kindermann W: Physical performance and serum potassium under chronic beta blockade. Eur J Appl Physiol 54:350–354, 1985
  24. Gordon RD, Kuchel O, Liddle GW, Island DP: Role of sympathetic nervous system in regulating renin and aldosterone production in man. J Clin Invest 46:599–605, 1967
  25. Ross EJ: Biological properties: Effects on the kidney, in Aldosterone and Aldosteronism London, Lloyd-Luke, 1975, pp. 74–92
  26. Goldberg AP, Geltman EM, Hagberg JM, Gavin GR, Delmez JA, Carney RM, Naumowicz A, Oldfield MH, Harter HR: Therapeutic benefits of exercise training for hemodialysis patients. Kidney Int 24 (Suppl 16):S303–S309, 1983
  27. Zabetakis PM, Gleim GW, Pasternack FL, Saraniti A, Nicholas JA, Michelis MF: Long-duration submaximal exercise conditioning in hemodialysis patients. Clin Nephrol 18:17–22, 1982 | PubMed | ISI | ChemPort |

Extra navigation

.
ADVERTISEMENT