Adrenoceptors mediating the cardiovascular and metabolic effects of alpha-methylnoradrenaline in humans.

alpha-Methylnoradrenaline is a widely used tool to study alpha2-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 alpha-methylnoradrenaline in humans, we have performed graded i.v. infusions of alpha-methylnoradrenaline in a randomized, placebo-controlled crossover study in six young, healthy males in the absence and presence of the beta-adrenoceptor antagonist propranolol, the alpha1-adrenoceptor antagonist doxazosin, and the alpha2-adrenoceptor antagonist yohimbine. alpha-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 alpha-methylnoradrenaline primarily acts on beta-adrenoceptors in the human cardiovascular and metabolic system, but an alpha2-adrenergic component of the response is detectable for changes of plasma noradrenaline, blood glucose, and serum insulin. Whereas alpha-methylnoradrenaline is selective for alpha2- over alpha1-adrenoceptors, beta-adrenoceptor blockade is required to unmask alpha-adrenoceptor-mediated vasoconstriction.