(MRC Group in Experimental Cardiology).

Background: Although β-adrenoceptors and adenylyl cyclase are known to be affected upon exposing cardiac membranes to some oxyradical generating systems, the results are conflict-ing. Furthermore, functional significance of alterations in the β-adrenoceptor-adenylyl cyclase system in terms of changes in the inotropic responses to catecholamines is not clear. Methods and Results: The positive inotropic effect of isoproterenol was augmented on per-fusing the isolated rat hearts with xanthine (X) plus xanthine oxidase (XO) for 5 minutes but was attenuated by perfusion for 15 minutes. The isoproterenol-stimulated adenylyl cyclase activity in cardiac membranes showed an increase at 10 minutes and a decrease at 30 minutes perfusion of hearts with X plus XO. The density of β-adrenoceptors in cardiac membranes was reduced after 10 minutes and 30 minutes of perfusion with X plus XO, whereas the affin-ity of β-adrenoceptors was increased after 10 minutes and reduced after 30 minutes. Although β-adrenoceptors were unaltered by 10 minutes of perfusion with X plus XO, their affinity was increased and density was decreased by 30 minutes of perfusion. The agonist competition curves using isoproterenol indicated an increase in the number of coupled recep-tors in the high affinity state on 10 minutes of perfusion and an increase in the low affinit