Abstract 1553: Apelin, the Ligand for the Angiotensin Receptor-like 1, Directly Affects Cardiomyocyte Contractility and Electrophysiology
Apelin, the ligand for the angiotensin receptor like-1, has an important role in cardiovascular regulation. Apelin is a potent endogenous positive inotropic agent that may play a role in the pathogenesis of atrial fibrillation and heart failure. However, whether apelin acts directly on cardiomyocytes remains unknown. Rat adult ventricular myocytes from normal (N) and failing (F) hearts (ejection fraction < 30%) obtained 8 weeks after coronary artery ligation were enzymatically dissociated, superfused with Krebs solution containing 1 mM Ca (37 °C), and field stimulated at 1Hz. Sarcomere length was measured by Fourier analysis of digitised myocytes images (Ionoptix Co.USA). Cytoplasmic [Ca] and pH were monitored using Indo-1 or Fluo-4 and Carboxy-SNARF-1 fluorescence respectively. Apelin 16 (10 nM) significantly increased sarcomere shortening within 1 minute of superperfusion in both N and F myocytes to similar levels (150 ± 13 % of control, n=11; p<0.001 and 127± 28 % of control n=9; p<0.05, respectively). However, this effect was only transient and, contractility returned to baseline after 10 minutes. The early increase in shortening was not accompanied by increased Ca transient amplitude. Intracellular pH increased significantly after application of 10 nM apelin (ΔpH from control + 0.0686 ± 0.052, n=9; p<0.001). The effects of apelin on action potential propagation were also studied in monolayers of cultured neonatal rat cardiomyocytes. Spontaneous field potentials were recorded using multielectrode arrays (8x8 30 μm electrodes, interelectrode distance 200 μm, Multichannel Systems, Germany). Activation maps were derived from the local activation times and mean conduction velocity (CV) calculated. 10 nM apelin significantly increased CV (24.1 ± 2.2 cm/s vs 18.34 ± 1.4 cm/s n =5; p<0.05). We conclude that apelin has direct cardiomyocyte effects on the propagation of action potential and contractility.