Effects of agmatine on afterdepolarizations induced by isoproterenol in guinea pig papillary muscles

AIM: To study the effects of agmatine (Agm) on early afterdepolarizations ( EAD) and delayed afterdepolarizations (DAD) induced by isoproterenol (Iso) in guinea pig papillary muscles. METHODS: EAD and DAD were recorded using intracellular glass microelectrode technique. RESULTS: (1) EAD and DAD indu ced by Iso 20 nmol.L-1 were markedly inhibited by pretreatment with Agm 1.0 - 2.0 mmol L-1 in a concentration-dependent manner. (2) N-G-nitro-L-argini ne methyl ester (L-NAME, 0.5 mmol.L-1), a NOS inhibitor, did not affect the inhibitory effects of Agm (1.0 mmol.L-1) on EAD and DAD induced by Iso. (3 ) The inhibitory effects of Agm (1.0 mmol L-1) on EAD and DAD induced by Is o (20 nmol L-1) were eliminated by pretreatment with idazoxan (Ida, 0.1 mmo l.L-1), an alpha-2 adrenergic receptor (alpha(2)-AR) and imidazoline recept or (IR) antagonist. CONCLUTION: The inhibitory effects of Agm on EAD and DA D induced by Iso in papillary muscles is related to the reduction in calciu m influx and mediated by alpha(2)-AR and/or IR.