Vol. 289, Issue 2, 918-925, May 1999

Adrenoceptors Mediating the Cardiovascular and Metabolic Effects of -Methylnoradrenaline in Humans¹

Rafael F. Schäfers, Jens Nürnberger, Burghard Herrmann, Rene R. Wenzel, Thomas Philipp and Martin C. Michel

Department of Medicine, University of Essen, Essen, Germany

-Methylnoradrenaline is a widely used tool to study ₂-adrenoceptor function, but its selectivity for this receptor has not been validated in humans in vivo. To characterize the adrenoceptors mediating cardiovascular and metabolic effects of -methylnoradrenaline in humans, we have performed graded i.v. infusions of -methylnoradrenaline in a randomized, placebo-controlled crossover study in six young, healthy males in the absence and presence of the -adrenoceptor antagonist propranolol, the ₁-adrenoceptor antagonist doxazosin, and the ₂-adrenoceptor antagonist yohimbine. -Methylnoradrenaline dose-dependently increased heart rate, systolic blood pressure, cardiac output, blood glucose, serum insulin, free fatty acids, and gastrin, shortened the duration of heart rate-corrected electromechanical systole, and decreased diastolic blood pressure, total peripheral resistance, and plasma noradrenaline. Propranolol completely reversed the rise in heart rate and cardiac output, the fall in peripheral resistance, the shortening of electromechanical systole, and the rise in insulin; it blunted the increase in free fatty acids and gastrin. Yohimbine did not significantly influence most parameters but significantly potentiated the rise in insulin, blunted the increase in glucose, and prevented the fall in noradrenaline. Doxazosin was largely without effect on any of these parameters. We conclude that i.v. administered -methylnoradrenaline primarily acts on -adrenoceptors in the human cardiovascular and metabolic system, but an ₂-adrenergic component of the response is detectable for changes of plasma noradrenaline, blood glucose, and serum insulin. Whereas -methylnoradrenaline is selective for ₂- over ₁-adrenoceptors, -adrenoceptor blockade is required to unmask -adrenoceptor-mediated vasoconstriction.