Myocardial calcium-independent nitric oxide synthase activity is present in dilated cardiomyopathy, myocarditis, and postpartum cardiomyopathy but not in ischaemic or valvar heart disease

Abstract

Objective: To determine the activity of the calcium-dependent constitutive (cNOS) and calcium-independent inducible nitric oxide (iNOS) synthases in heart tissue from patients with different cardiac diseases. Patients and design: Endomyocardial biopsy specimens were obtained from patients with dilated hearts (by echocardiography and ventriculography) and normal coronary arteries (by selective angiography). Recognised clinical, radiological, and histopathological criteria were used to diagnose non-inflammatory dilated cardiomyopathy (DCM) (n = 6), inflammatory cardiomyopathy (ICM) (n = 5), and peripartum cardiomyopathy (PPCM) (n = 3). Comparative groups were chosen with similarly dilated hearts caused by ischaemic (n = 5) or valvar disease (n = 4), and, in addition, non-dilated hearts with ischaemic (n = 5) and valvar (n = 3) disease. Venous blood was taken at the time of myocardial biopsy for assay of plasma tumour necrosis factor alpha (TNFα). Results: Myocardial tissue from patients with DCM, ICM, and PPCM showed considerable iNOS activity (16.8 (2.7) pmol citrulline/mg protein/min) with little or no cNOS activity (1.3 (0.9) pmol citrulline/mg protein/min). In contrast, myocardial tissue from patients with both dilated and non-dilated hearts of ischaemic or valvar aetiology showed cNOS and little, if any, iNOS activity (dilated - cNOS 11.7 (2.4) and iNOS 0.8 (0.6) pmol citrulline/mg protein/min; non-dilated - cNOS 12.1 (1.8) and iNOS 1.4 (0.8) pmol citrulline/mg protein/min). Plasma TNFα was detectable only in patients with inflammatory DCM. Conclusions: These results support the hypothesis the generation of nitric oxide by iNOS accounts for some of the dilatation and impaired contractility associated with inflammatory and non-inflammatory dilated cardiomyopathy and peripartum cardiomyopathy.