Anti-arrhythmic and electrophysiological effects of the endothelin receptor antagonists, BQ-123 and PD161721

Area of Science:

• Cardiovascular Pharmacology
• Cardiac Electrophysiology
• Endothelin Receptor Antagonism

Background:

• Ischaemia-induced arrhythmias pose a significant clinical challenge.
• Endothelin receptors (ET(A) and ET(A/B)) are implicated in cardiovascular regulation.
• Understanding novel anti-arrhythmic mechanisms is crucial for therapeutic development.

Purpose of the Study:

• To investigate the effects of endothelin ET(A) (BQ-123) and ET(A/B) (PD161721) receptor antagonists on ischaemia-induced arrhythmias.
• To evaluate the impact of these antagonists on maximum following frequency in cardiac tissue.

Main Methods:

• Langendorff perfused rat hearts were subjected to coronary artery occlusion to induce arrhythmias.
• Severity of arrhythmias, coronary perfusion pressure, and heart rate were measured.
• Maximum following frequency was assessed in isolated guinea-pig atria under varying extracellular potassium concentrations.

Main Results:

• BQ-123 and PD161721 significantly reduced the incidence of irreversible ventricular fibrillation from 58% to 0% in rat hearts.
• Both antagonists decreased maximum following frequency in guinea-pig atria, an effect not potentiated by elevated extracellular potassium.
• This contrasts with lignocaine, whose effect on maximum following frequency was potentiated by elevated extracellular potassium.

Conclusions:

• BQ-123 and PD161721 exhibit anti-fibrillatory effects in isolated rat hearts.
• This anti-arrhythmic action may be partly mediated by a reduction in maximum following frequency.
• The mechanism is unlikely to involve sodium channel blockade due to the lack of potentiation by elevated extracellular potassium.