Genistein potentiates the relaxation induced by beta(1)- and beta(2)-adrenoceptor activation in rat aortic rings

In rat aortic rings, genistein, an inhibitor of tyrosine kinase, but not da idzein, an inactive analogue of genistein, potentiated the relaxation induc ed by isoproterenol. Atenolol, a beta(1)-adrenoceptor antagonist, or ICI-11 8,551, a beta(2)-adrenoceptor antagonist, inhibited the relaxation induced by isoproterenol. The potentiating effect of genistein on the relaxation in duced by isoproterenol in the presence of ICI-118,551 was apparently greate r than that in the presence of atenolol. In the presence of ICI-118,551, th eophylline, an inhibitor of cyclic adenosine monophosphate (cAMP)-dependent phosphodiesterase (cAMP-PDE), markedly inhibited the potentiating effect o f genistein on the isoproterenol-induced relaxation, whereas in the presenc e of atenolol, theophylline only partly inhibited the potentiating effect o f genistein. The relaxation induced by forskolin, an activator of adenylyl cyclase, was potentiated by genistein or theophylline. In the presence of t heophylline, the relaxation induced by forskolin was not further affected b y genistein. Genistein also inhibited the activities of cAMP-PDE. In the pr esence of atenolol, but not ICI-118,551, iberiotoxin, an inhibitor of Ca-ac tivated K channels, inhibited the relaxation induced by isoproterenol and t he potentiating effect of genistein. In the presence of atenolol, quinacrin e, an inhibitor of phospholipase A(2), and metyrapone, an inhibitor of P-45 0 enzymes, but not alpha-naphthoflavone, an inhibitor of P-450 enzymes, ind omethacin, a cyclooxygenase inhibitor, or AA861, a 5-lipoxygenase inhibitor , inhibited the potentiating effect of genistein, These results suggest tha t the potentiation of the beta(1)-adrenoceptor-induced relaxation by activa tion of genistein may mostly be due to inhibition of cAMP-PDE activities. I n addition, the potentiation of the relaxation induced by activation of bet a(2)-adrenoceptors by genistein may be related to the inhibition of arachid onic acid metabolism and cAMP-PDE activities.