779-6 Human Inducible Nitric Oxide Synthase is Expressed in Dilated Cardiomyopathy, Valvular and Ischemic Heart Disease

Abstract

Nitric oxide is known to exert negative inotropic effects on myocytes. Initial reports using activity assays have suggested increased generation of nitric oxide in myocardium from patients with dilated cardiomyopathy and acute myocarditis. However, myocardial detection of mRNA encoding the cytokine-inducible form of nitric oxide synthase(iNOS) has not been reported in patients with heart failure. We extracted total RNA from right ventricular myocardium obtained from 40 human hearts; explanted hearts—dilated cardiomyopathy (n = 10), ischemic head disease (n = 10); intra-operative biopsies in patients with compensated heart failure - valvular heart disease (n = 9) ischemic heart disease (n = 1); and necropsy specimens (within 6 hours of death) from subjects who had suffered sudden death from a non-cardiac cause (n = 10). Samples were analyzed using reverse transcription — polymerase chain reaction (RT-PCR). Three pairs of oligonucleotide primers were used that were specific for iNOS, atrial natriuretic peptide (ANP) and human skeletal alpha actin. Expression of ANP in human ventricular myocardium has been shown to be a marker of changes in gene expression associated with heart failure and ventricular remodeling, and human skeletal alpha actin was used as an internal standard to indicate the presence of non-degraded mRNA. Controls Valvular HD DCM IHD iNOS 1/10 9/9 6/10 7/11 ANP 0/10 9/9 10/10 11/11 Human skeletal alpha actin expression was present in all samples. The frequency of iNOS expression was increased (p < 0.02) in right ventricular tissue from patients with head failure irrespective of etiology. Although this phenomenon might result from the effects of drug therapy and/or cardiac surgical procedures, it may be that expression of iNOS, like ANP, is part of the molecular phenotype of the failing heart. Local generation of increased levels of nitric oxide may contribute to contractile impairment in patients with valvular and ischemic head disease as well as in patients with dilated cardiomyopathy.