Metabolic and circulatory responses to selective adrenergic stimulation and blockade.

INDIRECT EVIDENCE has long supported the idea that catecholamines play an important role in fat metabolism." 2 Direct evidence for this was obtained in 1956, when investigators, Dole3 and Gordon and Cherkes,4 working independently, demonstrated that the intravenous infusion of aqueous epinephrine in humans results in a significant rise in the level of plasma free fatty acids (FFA). This response has also been observed after the intravenous administration of norepinephrine5 and isoproterenol6 7 and has been successfully blocked by a variety of agents.5 8.9 In 1948, Ahlquist'0 proposed that two distinct adrenergic receptors, alpha and beta, mediate the neuromuscular responses to sympathomimetic amines. Subsequent work has confirmed this hypothesis, permitting classification of adrenergic agents on the basis of their neuromuscular activity. In contrast, investigations attempting to demonstrate that the metabolic responses to sympathomimetic amines are also mediated by alpha and beta receptors of the type proposed by Ahlquist have been confusing." In 1962, Pilkington and associates'2 demonstrated that administration of a new selective beta-adrenergic blocking agent, pronethalol, effectively blocked subsequent mobilization of FFA by epinephrine and that a well-known alpha-adrenergic blocking agent, phenoxybenzamine, failed to block this effect. With this evidence, Pilkington and co-workers suggested