A new medication for the treatment of heart failure may be the peptide adrenomedullin, which has vasodilatory, natriuretic, and diuretic properties. Atrial Fibrillation (AF) is linked to a higher risk of heart failure, however it is yet unknown how adrenomedullin affects the development of atrial arrhythmia. This study looked into whether adrenomedullin affects the electrophysiology of the Pulmonary Vein (PV) or the atria. The effects of adrenomedullin (10 pg/mL, 30 pg/mL, and 100 pg/mL) on the electrical activity, mechanical responsiveness, and ionic currents of isolated rabbit PV and sinoatrial node tissue preparations as well as single PV cardiomyocytes were investigated using conventional microelectrode or whole-cell patch clamps. Adrenomedullin dramatically decreased the PVs' spontaneous beating rate from 2.0 Hz to 1.3 Hz and 1.1 Hz at concentrations of 30pg/mL and 100 pg/mL (reductions of 32.9% 7.1% and 44.9 8.4%, respectively). It also decreased the PVs' diastolic tension by 12.8% 4.1% and 14.5% 4.1%, respectively. Adrenomedullin, in contrast, had no impact on the beating of the sinoatrial node. Adrenomedullin (30 pg/mL) had no effect on the PVs' spontaneous beating rate or diastolic tension when L-NAME was present. Adrenomedullin (30 pg/mL) dramatically decreased the sodium-calcium exchanger's reverse-mode current and L-type Calcium Current (ICa-L) in the single-cell studies. Adrenomedullin may be helpful for treating atrial tachyarrhythmia as it decreases spontaneous PV activity and PV diastolic tension by reducing ICa-L and NCX current.
