BETA-1-ADRENOCEPTOR AND BETA-2-ADRENOCEPTOR-MEDIATED RELAXATION IN HUMAN INTERNAL MAMMARY ARTERY AND SAPHENOUS-VEIN - UNCHANGED BETA-ADRENOCEPTOR AND ALPHA-ADRENOCEPTOR RESPONSIVENESS AFTER CHRONIC BETA-1-ADRENOCEPTOR BLOCKADE

1 We have recently reported that patients taking beta1-adrenoceptor-se lective antagonists exhibit marked sensitization of beta2-adrenoceptor responses but unaltered beta1-adrenoceptor responses in the heart, bo th in vitro and in vivo. We therefore investigated beta1- and beta2-ad renoceptor-mediated relaxant responses in rings of human internal mamm ary artery and saphenous vein without endothelium, taken from beta1-bl ocked and non-beta-blocked patients undergoing coronary artery bypass graft surgery, for comparison. We also examined alpha1-adrenoceptor-me diated contraction in these vessels, to determine whether beta1-blocka de had any cross-regulatory effect. 2 Following alpha-blockade with 10 muM phenoxybenzamine, both noradrenaline and adrenaline produced conc entration-dependent relaxations in both blood vessels, their effects b eing mediated predominantly through beta2-adrenoceptors; a lesser beta 1-adrenoceptor component to relaxation was also found in internal mamm ary artery and a minor beta1-adrenoceptor component was present in sap henous vein. No differences were found in beta1- or in beta2-adrenocep tor-mediated vasorelaxation between beta1-blocked and non-beta-blocked patients. 3 Methoxamine produced concentration-dependent contractions in both blood vessels, and the potency and efficacy were not signific antly different between vessels from beta1-blocked and from non-beta-b locked patients. 4 These findings indicate that, in these tissues, whi ch possess a relatively minor beta1-adrenoceptor component in contrast to myocardial tissue, chronic beta1-blocker treatment does not alter either beta1- or beta2-adrenoceptor responses. Likewise, in such tissu es, alpha1-adrenoceptor responses are unaffected by prior beta1-blocka de.