MYOCARDIAL ELECTROPHYSIOLOGICAL PROPERTIES IN THE PRESENCE OF AN AT(1) ANGIOTENSIN-II RECEPTOR ANTAGONIST

Introduction. Blockade of the AT(1) angiotensin LT (Ang II) receptor h as been shown to provide antihypertensive effects. However, whether AT I Ang II receptor antagonists influence myocardial electrophysiologica l properties remains unclear. Methods and results. Accordingly, atrial and ventricular myocardial electrophysiological properties were exami ned in adult rat (n = 13) and guinea pig (n = 9) myocardial preparatio ns in the presence of the specific AT(1) Ang II receptor antagonist, v alsartan (CGP 48933; 0.5, 5, or 500 mu mol/L). These concentrations re flect up to 100 fold higher drug concentrations than those observed in clinical trials. Transmembrane potential data were recorded using sta ndard microelectrode techniques at baseline and following superfusion with valsartan. The lower concentrations of valsartan (0.5 and 5 mu mo l/L) had minimal effects on myocardial electrophysiology. In the prese nce of 500 mu mol/L of valsartan, resting membrane potential increased from baseline in both rat (-82.3 +/- 4.1 vs -76.8 +/- 5.8 mV, p < 0.0 5) 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 incr eased 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) myocard ium following exposure to 500 mu mol/L of valsartan. In a separate ser ies of experiments, Ang II (1.0 mu mol/L) had no effect on atrial or v entricular action potential characteristics in either species. Conclus ion. Thus, the effects of valsartan, which were observed only at conce ntrations 100 fold higher than those reported in clinical trials, may be due to non-specific drug interactions with the myocyte sarcolemma.