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Electrophysiological Effects of Nipradilol (K-351) on Isolated Rabbit Hearts and Guinea Pig Ventricular Muscles

Summary: 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 >10−5M 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 (FRPAV), and effective refractory period of ventricular muscle (ERPVM) 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, and ERPVM were inhibited competitively by pretreatment with nipradilol at >10−8M. 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 >10−5M caused a decrease of the maximum upstroke velocity (&OV0312;max) 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 &OV0312;max 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 β-adrenocepter blocking action and, at extremely high concentrations, quinidine-like inhibitory effects on the cardiac excitability and conductivity.