Piceatannol, a derivative of resveratrol, moderately slows l Na inactivation and exerts antiarrhythmic action in ischaemia-reperfused rat hearts

Abstract

Background and purpose: Piceatannol is more potent than resveratrol in free radical scavenging in association with antiarrhythmic and cardioprotective activities in ischaemic-reperfused rat hearts. The present study aimed to investigate the antiarrhythmic efficacy and the underlying ionic mechanisms of piceatannol in rat hearts. Experimental approach: Action potentials and membrane currents were recorded by the whole-cell patch clamp techniques. Fluo-3 fluorimetry was used to measure cellular Ca 2+ transients. Antiarrhythmic activity was examined from isolated Langendorff-perfused rat hearts. Key results: In rat ventricular cells, piceatannol (3-30 μmol-L -1) prolonged the action potential durations (APDs) and decreased the maximal rate of upstroke (V max) without altering Ca 2+ transients. Piceatannol decreased peak I na and slowed I Na inactivation, rather than induced a persistent non-inactivating current, which could be reverted by lidocaine. Resveratrol (100 μmol-L -1) decreased peak I Na without slowing I Na inactivation. The inhibition of peak I Na or V max was associated with a negative shift of the voltage-dependent steady-state I Na inactivation curve without altering the activation threshold. At the concentrations more than 30 μmol-L -1, piceatannol could inhibit I Ca,L, I to, I kr, Ca 2+ transients and Na +-Ca 2+ exchange except I K1. Piceatannol (1-10 μmol-L -1) exerted antiarrhythmic activity in isolated rat hearts subjected to ischaemia-reperfusion injury. Conclusions and implications: The additional hydroxyl group on resveratrol makes piceatannol possessing more potent in I Na inhibition and uniquely slowing I Na inactivation, which may contribute to its antiarrhythmic actions at low concentrations less than 10 μmol-L -1. © 2009 The British Pharmacological Society All rights reserved.