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


METHODS
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 (TNF alpha).


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 TNF alpha 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.
D000328:Adult; D001024:Aortic Valve Stenosis / Q000201:enzymology; D002118:Calcium / Q000378:metabolism*; D002311:Cardiomyopathy, Dilated / Q000201:enzymology / Q000276:immunology; D005260:Female; D006331:Heart Diseases / Q000201:enzymology*; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000201:enzymology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D002118:Calcium