nNOS deficiency in mice significantly increased 30-day mortality and the incidence of ventricular arrhythmias and fibrillation after myocardial infarction compared with wild-type mice.
Does nNOS deficiency increase ventricular arrhythmia and mortality after myocardial infarction in mice?
Neuronal nitric oxide synthase (nNOS) deficiency increases ventricular arrhythmia and mortality after myocardial infarction in mice by altering L-type Ca2+ channel activity and Ca2+ handling.
BACKGROUND: Neuronal nitric oxide synthase (nNOS) is expressed in cardiomyocytes and plays a role in regulating cardiac function and Ca2+ homeostasis. However, the role of nNOS in cardiac electrophysiology after myocardial infarction (MI) is unclear. We hypothesized that nNOS deficiency increases ventricular arrhythmia and mortality after MI. METHODS AND RESULTS: MI was induced in wild-type (WT) or nNOS(-/-) mice by ligation of the left coronary artery. Thirty-day mortality was significantly higher in nNOS(-/-) compared with WT mice. Additionally, nNOS(-/-) mice had impaired cardiac function 2 days after MI. Telemetric ECG monitoring showed that compared with WT, nNOS(-/-) mice had significantly more ventricular arrhythmias and were more likely to develop ventricular fibrillation after MI. Treatment with the L-type Ca2+ channel blocker verapamil reduced the incidence of arrhythmia and ventricular fibrillation in nNOS(-/-) mice after MI. To assess the role of nNOS in Ca2+ handling, patch-clamp and Ca2+ fluorescence techniques were used. Ca2+ transients and L-type Ca2+ currents were higher in nNOS(-/-) compared with WT cardiomyocytes. Additionally, nNOS(-/-) cardiomyocytes exhibited significantly higher systolic and diastolic Ca2+ over a range of pacing frequencies. Treatment with the NO donor S-nitroso N-acetyl-penicillamine decreased Ca2+ transients and L-type Ca2+ current in both nNOS(-/-) and WT cardiomyocytes. Furthermore, S-nitrosylation of Ca2+ handling proteins was significantly decreased in nNOS(-/-) myocardium after MI. CONCLUSIONS: Deficiency in nNOS increases ventricular arrhythmia and mortality after MI in mice. The antiarrhythmic effect of nNOS involves inhibition of L-type Ca2+ channel activity and regulation of Ca2+ handling proteins via S-nitrosylation.
Burger et al. (Mon,) conducted a other in Myocardial infarction. nNOS deficiency vs. Wild-type (WT) mice was evaluated on 30-day mortality and ventricular arrhythmias. nNOS deficiency in mice significantly increased 30-day mortality and the incidence of ventricular arrhythmias and fibrillation after myocardial infarction compared with wild-type mice.