Abnormal diastolic currents in ventricular myocytes from spontaneous hypertensive heart failure rats

Abnormal diastolic currents in ventricular myocytes from spontaneous hypertensive heart failure rats. Am J Physiol Heart Circ Physiol 291: H2192-H2198, 2006. First published June 9, 2006; doi:10.1152/ajpheart.01146.2005. - 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 (I-K1) and expression of pacemaker current (I-f) 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 I-K1 was significantly reduced at both 8 and >= 17 mo in SHHF rats compared with controls. There was a reduction in inward I-K1 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 I-f. Action potential recordings in the SHHF rats demonstrated abnormal automaticity, which was abolished by the addition of an I-f blocker (10 mu M zatebradine). Increased I-f during hypertension alone or combined increases in I-f with reduced I-K1 during the progression to hypertensive heart failure contribute to a substrate for arrhythmogenesis.