Hypokalemia from beta2-receptor stimulation by circulating epinephrine

Area of Science:

• Pharmacology
• Endocrinology
• Cardiovascular Physiology

Background:

• Epinephrine (adrenaline) is a hormone and neurotransmitter with diverse physiological effects.
• Hypokalemia, a decrease in plasma potassium levels, can have serious clinical consequences.
• The specific mechanisms and physiological relevance of epinephrine-induced hypokalemia require further elucidation.

Purpose of the Study:

• To investigate if beta2-adrenoceptor stimulation mediates epinephrine-induced hypokalemia.
• To determine if hypokalemia occurs at physiologically relevant epinephrine concentrations.
• To differentiate the beta2-mediated effects of epinephrine from its other actions.

Main Methods:

• Infusion of epinephrine into healthy volunteers to achieve specific circulating concentrations.
• Administration of isoproterenol, a non-selective beta-agonist, for comparison.
• Use of a selective beta2-receptor antagonist (ICI 118551) to block beta2-adrenoceptor effects.
• Measurement of plasma potassium, insulin, renin activity, glucose, and heart rate.

Main Results:

• Epinephrine infusion led to hypokalemia, decreased plasma insulin, elevated plasma renin activity, and tachycardia.
• Isoproterenol caused tachycardia and increased renin activity but not hypokalemia.
• A selective beta2-receptor antagonist prevented epinephrine-induced hypokalemia but only partially affected other responses.
• Fifteen- to 30-fold increases in epinephrine concentration were associated with hypokalemia via a specific beta2-receptor effect.

Conclusions:

• Epinephrine-induced hypokalemia is mediated by beta2-adrenoceptor stimulation.
• This beta2-specific effect is distinct from other actions of epinephrine, such as tachycardia or renin release.
• The findings suggest that epinephrine-induced hypokalemia may be physiologically significant, particularly in conditions like severe myocardial infarction.