β 1 ‐ and β 2 ‐adrenoceptor‐mediated relaxation in human internal mammary artery and saphenous vein: unchanged β‐ and α‐adrenoceptor responsiveness after chronic β 1 ‐adrenoceptor blockade

1 We have recently reported that patients taking β 1 ‐adrenoceptor‐selective antagonists exhibit marked sensitization of β 2 ‐adrenoceptor responses but unaltered β 1 ‐adrenoceptor responses in the heart, both in vitro and in vivo . We therefore investigated β 1 ‐ and β 2 ‐adrenoceptor‐mediated relaxant responses in rings of human internal mammary artery and saphenous vein without endothelium, taken from β 1 ‐blocked and non‐β‐blocked patients undergoing coronary artery bypass graft surgery, for comparison. We also examined α 1 ‐adrenoceptor‐mediated contraction in these vessels, to determine whether β 1 ‐blockade had any cross‐regulatory effect. 2 Following α‐blockade with 10 μ m phenoxybenzamine, both noradrenaline and adrenaline produced concentration‐dependent relaxations in both blood vessels, their effects being mediated predominantly through β 2 ‐adrenoceptors; a lesser β 1 ‐adrenoceptor component to relaxation was also found in internal mammary artery and a minor β 1 ‐adrenoceptor component was present in saphenous vein. No differences were found in β 1 ‐ or in β 2 ‐adrenoceptor‐mediated vasorelaxation between β 1 ‐blocked and non‐β‐blocked patients. 3 Methoxamine produced concentration‐dependent contractions in both blood vessels, and the potency and efficacy were not significantly different between vessels from β 1 ‐blocked and from non‐β‐blocked patients. 4 These findings indicate that, in these tissues, which possess a relatively minor β 1 ‐adrenoceptor component in contrast to myocardial tissue, chronic β 1 ‐blocker treatment does not alter either β 1 ‐ or β 2 ‐adrenoceptor responses. Likewise, in such tissues, α 1 ‐adrenoceptor responses are unaffected by prior β 1 ‐blockade.