Myocardial electrophysiological properties in the presence of an AT1 angiotensin II receptor antagonist.
BACKGROUND
Blockade of the AT1 angiotensin II (Ang II) receptor has been shown to provide anti-hypertensive effects. However, whether AT1 Ang II receptor antagonists influence myocardial electrophysiological properties remains unclear.


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 AT1 Ang II receptor antagonist, valsartan (CGP 48933; 0.5, 5, or 500 mumol/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 mumol/L) had minimal effects on myocardial electrophysiology. In the presence of 500 mumol/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 mumol/L of valsartan. In a separate series of experiments, Ang II (1.0 mumol/L) had no effect on atrial or ventricular action potential characteristics in either species.


CONCLUSIONS
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.
Cox
M H
MH
Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston 29425, USA.
O
S J
SJ
de Gasparo
M
M
Mukherjee
R
R
Hewett
K W
KW
Spinale
F G
FG
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D004594:Electrophysiology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D057911:Angiotensin Receptor Antagonists; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine