1 This study was designed to investigate the mechanism(s) of the negative inotropic effects of α1-adrenoceptor agonists observed in rat isolated left atria after exposure to free radicals. 2 Ouabain and calphostin C were used in contraction experiments to block the sodium pump and protein kinase C. Methoxamine-induced phospholipase C and Na+/K+ ATPase activities were measured. 3 Methoxamine (300 μM) increased contractile force by 1.6±0.2 mN in control atria but decreased contractile force in electrolysis-treated atria by 2.0±0.1 mN (P