Electrophysiological effects of nipradilol (K-351) on isolated rabbit hearts and guinea pig ventricular muscles.

Effects of nipradilol (K-351), a newly developed antihypertensive agent, on electrophysiological properties of the heart were examined in Langendorff-perfused rabbit hearts and in superfused guinea pig ventricular muscles. In rabbit hearts, nipradilol at concentrations greater than 10(-5) M caused a significant prolongation of atrio-His bundle conduction time (AH) as well as His bundle-ventricular conduction time (HV), whereas heart rate (HR), functional refractory period of atrioventricular node (FRPVM) were unaffected. The intensity of the negative dromotropic effect of nipradilol was less than half that of propranolol. Isoproterenol-induced increase in HR and a shortening of AH, FRPAV, ERPVM were inhibited competitively by pretreatment with nipradilol at greater than 10(-8) M. Nipradilol was about two to three times more potent than propranolol in antagonizing isoproterenol-induced effects. In guinea pig ventricular muscles, nipradilol at a concentration greater than 10(-5) M caused a decrease of the maximum upstroke velocity (VMAX) of the action potential without affecting resting potential and action potential duration. In the presence of nipradilol, trains of stimuli at rates higher than 0.2 Hz led to an exponential decline in VMAX to achieve a new plateau. The time constant for the recovery from use-dependent block was 4.3 s. These findings suggest that nipradilol may have a potent cardiac beta-adrenoceptor blocking action and, at extremely high concentrations, quinidine-like inhibitory effects on the cardiac excitability and conductivity.