Interaction between alpha- and beta-adrenoceptor-mediated cardiovascular effects.

Abstract

A survey is given of the mutual interaction of alpha- and beta-adrenoceptor mediated cardiovascular effects, with an emphasis on the effects of drugs which simultaneously block alpha- and beta-adrenoceptors. This discussion is preceded by a review of the various subtypes of adrenoceptors, including pre/postsynaptic, alpha 1/alpha 2- and beta 1/beta 2-receptors with an emphasis on their various selective agonists and antagonists and their functional aspects. For drugs which display comparable degrees of alpha- and beta-adrenoceptor blockade the following effects may be anticipated: vasodilatation, a reduction in total peripheral resistance (TPR) and a decrease in blood pressure, as a result of postsynaptic (alpha 1 + alpha 2) adrenoceptor blockade; a fall in blood pressure as a result of beta-receptor blockade; no reflex tachycardia in spite of the vasodilatation (alpha 1 + alpha 2 blockade) owing to beta-receptor blockade. For a drug which simultaneously blocks alpha 2- and beta 1-adrenoceptors the following effects may be anticipated: all cardiac changes usually induced by beta 1-blockade (reduced heart rate, contractility and A-V conduction); vasodilatation induced by postsynaptic alpha 2-adrenoceptor blockade; enhanced release of presynaptic noradrenaline, owing to presynaptic alpha 2-receptor blockade. Celiprolol is an example of a drug which combines alpha 2- and beta 1-adrenoceptor blocking properties. It should be realized, however, that the alpha 2-receptor affinity of the drug is much lower than its beta 1-receptor antagonism, which probably dominates the drug's profile.