Myocardial electrophysiological properties in the presence of an AT 1 angiotensin II receptor antagonist

Introduction Blockade of the AT 1 angiotensin II (Ang II) receptor has been shown to provide antihypertensive effects. However, whether AT 1 Ang II receptor antagonists influence myocardial electrophysiological properties remains unclear. Methods and results Accordingly, atrial and ventricular myocardial electrophysiological properties were examined in adult rat (n=13) and guinea pig (n=9) myocardial preparations in the presence of the specific AT 1 Ang II receptor antagonist, valsartan (CGP 48933; 0.5, 5, or 500 μmol/L). These concentrations reflect up to 100 fold higher drug concentrations than those observed in clinical trials. Transmembrane potential data were recorded using standard microelectrode techniques at baseline and following superfusion with valsartan. The lower concentrations of valsartan (0.5 and 5 μmol/L) had minimal effects on myocardial electrophysiology. In the presence of 500 μmol/L of valsartan, resting membrane potential increased from baseline in both rat (−82.3±4.1 vs −76.8±5.8 mV, p<0.05) and guinea pig (−81.6±2.9 vs −76.9±2.0 mV, p<0.05) atrial myocardium. Action potential duration at 90% repolarization was increased in guinea pig atrial (91.7±1.4 vs 80.0±5.6 ms, p<0.05) and ventricular (131.1±8.1 vs 118.7±8.3 ms, p<0.05) myocardium following exposure to 500 μmol/L of valsartan. In a separate series of experiments Ang II (1.0 μmol/L) had no effect on atrial or ventricular action potential characteristics in either species. Conclusion Thus, the effects of valsartan, which were observed only at concentrations 100 fold higher than those reported in clinical trials, may be due to non-specific drug interactions with the myocyte sarcolemma.