Epinephrine-induced hypokalemia: the role of beta adrenoceptors

Epinephrine was infused intravenously in 9 normal volunteers to plasma concentrations similar to those found after acute myocardial infarction. This study was undertaken on 3 occasions after 5 days of treatment with placebo or the ß-adrenoceptor antagonist, atenolol, which is relatively ß₁ selective, or timolol, which blocks both ß₁ and ß₂ receptors. Epinephrine increased the systolic blood pressure (BP), decreased the diastolic BP and increased the heart rate modestly. These changes were prevented by atenolol. However, after timolol the diastolic BP rose by +19 mm Hg and heart rate fell by -8 beats/min. Epinephrine caused the corrected QT interval to lengthen (0.36 ± 0.02 to 0.41 ± 0.06 second). No significant changes were found in the corrected QT interval when subjects were pretreated with atenolol or timolol. The serum potassium decreased from 4.06 to 3.22 mmol/liter after epinephrine. Serum potassium decreased to a lesser extent to 3.67 mmol/liter after atenolol and actually increased to 4.25 mmol/liter after timolol. In a further study with a similar design another nonselective ß blocker propranolol also increased potassium after epinephrine. While atenolol also prevented hypokalemia in this study, it did not block the ß₂-receptor mediated decrease in diastolic BP. Epinephrine-induced hypokalemia results from stimulation of a ß-adrenoceptor linked to membrane sodium/potassium adenosine triphosphatase causing potassium influx. This appears to be predominantly mediated by ß₂ receptors although ß₁ receptors may also play a part.