Beta 1- and beta 2-adrenoceptor-mediated relaxation in human internal mammary artery and saphenous vein: unchanged beta- and alpha-adrenoceptor responsiveness after chronic beta 1-adrenoceptor blockade.
1. We have recently reported that patients taking beta 1-adrenoceptor-selective antagonists exhibit marked sensitization of beta 2-adrenoceptor responses but unaltered beta 1-adrenoceptor responses in the heart, both in vitro and in vivo. We therefore investigated beta 1- and beta 2-adrenoceptor-mediated relaxant responses in rings of human internal mammary artery and saphenous vein without endothelium, taken from beta 1-blocked and non-beta-blocked patients undergoing coronary artery bypass graft surgery, for comparison. We also examined alpha 1-adrenoceptor-mediated contraction in these vessels, to determine whether beta 1-blockade had any cross-regulatory effect. 2. Following alpha-blockade with 10 microM phenoxybenzamine, both noradrenaline adrenaline produced concentration-dependent relaxations in both blood vessels, their effects being mediated predominantly through beta 2-adrenoceptors; a lesser beta 1-adrenoceptor component to relaxation was also found in internal mammary artery and a minor beta 1-adrenoceptor component was present in saphenous vein. No differences were found in beta 1- or in beta 2-adrenoceptor-mediated vasorelaxation between beta 1-blocked and non-beta-blocked patients. 3. Methoxamine produced concentration-dependent contractions in both blood vessels, and the potency and efficacy were not significantly different between vessels from beta 1-blocked and from non-beta-blocked patients. 4. These findings indicate that, in these tissues, which possess a relatively minor beta 1-adrenoceptor component in contrast to myocardial tissue, chronic beta 1-blocker treatment does not alter either beta 1- or beta 2-adrenoceptor responses. Likewise, in such tissues, alpha 1-adrenoceptor responses are unaffected by prior beta 1-blockade.
Ferro
A
A
Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital.
Kaumann
A J
AJ
Brown
M J
MJ
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D002395:Catecholamines / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008323:Mammary Arteries / Q000187:drug effects; D008729:Methoxamine / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D012501:Saphenous Vein / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D008729:Methoxamine