Nitric oxide synthase II mRNA expression in cardiac tissue of patients with heart failure undergoing cardiac transplantation

Objectives: To examine whether inducible nitric oxide synthase is expressed in myocardial tissue of patients with heart failure. Background: There is increasing evidence that alterations in nitric oxide s ynthesis are of pathophysiologic importance in heart failure. Nitric oxide (NO) can exert negative inotropic and cytotoxic effects on cardiomyocytes. A number of studies have shown altered nitric oxide production by the endot helial constitutive isoform of nitric oxide synthase (NOS III), but there i s little information on the role of NOS II. Expression of NOS II could lead to excessive production of NO in the myocardium and affect cardiac contrac tility. Methods: NOS II mRNA expression in myocardial tissue of 18 patients with id iopathic dilated cardiomyopathy (DCM), 7 patients with ischemic cardiopathy and severe ventricular dysfunction (ISCH), 4 patients with acute myocardia l infarction (AMI) and 11 controls. Serum concentration of NO2-/NO3- (NOx) was also measured. Results: NOS II gene expression occurred in all the patients with DCM, in 1 out of the 7 ISCH patients, in 2 out of the 4 patients with AMI and in non e of the controls. Moreover, DCM patients showed a significant 6-fold incre ase in NOx concentration (253 +/- 47 nm/ml) as compared to controls (40 +/- 2 nn/ml) P < 0.001, a phenomenon not observed in ISCH patients (56 +/- 3 n m/ml). Conclusions: NOS II expression occurs in failing human cardiac myocytes and can play an specific role in the pathogenesis of DCM.