Enhancement of Peripheral Alpha-Receptor Stimulation by Blockade of "Silent" Beta Receptors

Abstract

Evidence is presented for the existence of "silent" peripheral beta adrenergic receptors with which alpha-receptor stimulants might combine without producing measurable vasodilation. Addition of propranolol (1x10 -7 M) or MJ-1999 (5x10 -6 M) to Krebs solution perfusing canine isolated mesenteric arteries enhanced (1) the pressor responses to intra-arterially administered epinephrine, norepinephrine, and methoxamine and (2) the vasoconstrictor effects of perivascular sympathetic nerve stimulation. Enhancement of the pressor effects of epinephrine and norepinephrine was unaltered during cocaine or guanethidine potentiation. The doses of the beta-receptor blocking agents that enhanced pressor responses in isolated arteries were identical to those required to provide 80 to 100% blockade of the positive inotropic and chronotropic effects of epinephrine and norepinephrine in isolated rabbit hearts. Propranolol and MJ-1999 also enhanced the elevating effects of methoxamine on canine blood pressure. In higher concentrations, propranolol (1x10 -4 M) and MJ-1999 (1x10 -3 M) produced alpha-receptor blockade in the isolated arteries, and propranolol, but not MJ-1999, produced myocardial depression in isolated rabbit hearts. These data are interpreted as indicating that alpha-receptor stimulants usually combine with both peripheral alpha and beta adrenergic receptors, and blockade of the peripheral beta receptors makes more stimulant available for alpha-receptor stimulation.