More on Paradoxical Pressor Effects of Nonselective Beta-Blockers

Abstract

A pressor effect of nonselective beta-blockers has been reported from the very beginning [1]. It was observed in patients with emotional stress, low renin hypertension and increased sympathetic activity [2], also in patients with untreated pheochromocytoma [3], with clonidine withdrawal [4], abuse of cocaine [5], and subcutaneous administration of epinephrine [6]. The most consistent finding in these reports was the situation of increased sympathetic activity. It was hypothesized that alpha-receptor-mediated vasoconstriction unopposed by beta-2-receptor-mediated vasodilation might be responsible. In situations of increased sympathetic activity this mechanism might override the otherwise hypotensive activity of nonselective beta-blockers. In order to test this hypothesis investigators started to design controlled trials comparing beta-1-selective and nonselective beta-blockers. On the one hand beta-1-selective blockers have a weak binding potency at the beta-2-receptor site and are, thus, less likely to produce this pressor effect. On the other hand, however, the selectivity is not absolute, but dose-dependent (e.g., metoprolol and atenolol lose their beta-1-selectivity with incremental doses [7]). Correspondingly, the different effects of beta-1-selective drugs on peripheral vascular resistance compared to nonselective compounds seem to be dose dependent [8]. Finally, even the heart does contain not only socalled cardioselective beta-1 but also otherwise vasodilative beta-2-adrenergic receptors [9].