Chronic Treatment with N‐acetylcysteine (NAC) Improves Cardiovascular Function in Syrian Cardiomyopathic Hamsters

Abstract

It has been postulated that oxidative stress is a contributing factor in the onset and development of heart failure (HF). To further evaluate this point, one‐month‐old Syrian cardiomyopathic hamsters (SCH) were treated for a 5‐month period with N‐acetylcysteine (NAC, 1g/kg/day). Vascular responses for acetylcholine (Ach), norepinephrine (NE) and Ang II were assessed in aortic rings from 6‐month‐old treated and untreated SCH. Systolic blood pressure (SBP), superoxide production in aorta and heart tissue (determined by lucigenin), and echocardiographic parameters were also evaluated. Chronic treatment with NAC improved 24% (P<0.05) the Ach‐induced relaxation (EMax value from 45.8±4% to 56.1±2% n=7) but did not modify EC50 values, NE and Ang II‐induced contraction, or SBP. Vascular superoxide production was reduced 50% by NAC treatment. Cardiac superoxide concentration, however, remained unchanged (1281±94 cpm/mg vs. 1275±82 cpm/mg, P>0.05). Ejection fraction increased from 39±4% in untreated SCH to 57±4% (n=11, P<0.05), and left ventricular end‐diastolic and end‐systolic volumes significantly decreased (P<0.05). Cardiac output index improved although did not reach statistical significance. These results suggest that antioxidant therapy alone improves cardiovascular function but does not prevent the appearance of HF in this animal model. Supported by NIH 2 SO6‐GM 08224.