EXPRESSION OF INDUCIBLE NITRIC-OXIDE SYNTHASE IN FAILING AND NONFAILING HUMAN HEART

Recently, a significant activity of inducible nitric oxide synthase (i NOS) has been reported in biopsies from failing hearts due to idiopath ic dilated cardiomyopathy (IDC). Thus, a potential pathophysiological role of iNOS in IDC has been stated. In order to investigate, whether iNOS expression is of pathophysiological relevance in human heart fail ure, we measured iNOS protein expression and cGMP content in left vent ricular myocardium from non-failing and failing human hearts. Immunobl ot analysis revealed iNOS protein expression in four out of six failin g hearts from septic patients, whereas no iNOS-protein expression was detected in either non-failing human hearts (n=6) or failing hearts du e to IDC (n=9), ischemic heart disease (IHD, n=7), Becker muscular dys trophy (BMD, n=2) and mitoxantrone-induced toxic cardiomyopathy (TCM, n=1). cGMP content was increased by 130% in septic hearts, whereas the re was no cGMP increase in hearts with IDC, IHD and BMD compared to no n-failing hearts. We conclude, that the induction of iNOS may play a r ole in contractile dysfunction observed in septic shock, but is unlike ly to be of major pathophysiological importance in end-stage heart fai lure due to IDC, IHD, BMD and TCM. (C) 1996 Academic Press Limited