Hypertension is a common cause of heart failure, and ventricular arrhythmias are a major cause of death in heart failure. The spontaneous hypertension heart failure (SHHF) rat model was used to study altered ventricular electrophysiology in hypertension and heart failure. We hypothesized that a reduction in the inward rectifier K+ current ( IK1) and expression of pacemaker current ( If) would favor abnormal automaticity in the SHHF ventricle. SHHF ventricular myocytes were isolated at 2 and 8 mo of age and during end-stage heart failure (≥17 mo); myocytes from age-matched rats served as controls. Inward IK1 was significantly reduced at both 8 and ≥17 mo in SHHF rats compared with controls. There was a reduction in inward IK1 due to aging in the controls only at ≥17 mo. We found a significant increase in If at all ages in the SHHF rats, compared with young controls. In controls, there was an age-dependent increase in If. Action potential recordings in the SHHF rats demonstrated abnormal automaticity, which was abolished by the addition of an If blocker (10 μM zatebradine). Increased If during hypertension alone or combined increases in If with reduced IK1 during the progression to hypertensive heart failure contribute to a substrate for arrhythmogenesis.
Developmental changes in the pacemaker current and membrane currents of the guinea pig myocardium.
