Expression of inducible nitric oxide synthase in failing and non-failing human heart.
Recently, a significant activity of inducible nitric oxide synthase (iNOS) has been reported in biopsies from failing hearts due to idiopathic 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 failure, we measured iNOS protein expression and cGMP content in left ventricular myocardium from non-failing and failing human hearts. Immunoblot analysis revealed iNOS protein expression in four out of six failing hearts from septic patients, whereas no iNOS-protein expression was detected in either non-failing human hearts (n = 6) or failing hearts due to IDC (n = 9), ischemic heart disease (IHD, n = 7), Becker muscular dystrophy (BMD, n = 2) and mitoxantrone-induced toxic cardiomyopathy TCM, n = 1). cGMP content was increased by 130% in septic hearts, whereas there was no cGMP increase in hearts with IDC. IHD and BMD compared to non-failing hearts. We conclude, that the induction of iNOS may play a role in contractile dysfunction observed in septic shock, but is unlikely to be of major pathophysiological importance in end-stage heart failure due to IDC, IHD, BMD and TCM.
Thoenes
M
M
Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Hamburg.
Förstermann
U
U
Tracey
W R
WR
Bleese
N M
NM
Nüssler
A K
AK
Scholz
H
H
Stein
B
B
D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced / Q000201:enzymology* / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000201:enzymology; D002460:Cell Line; D006152:Cyclic GMP / Q000378:metabolism; D015870:Gene Expression; D006333:Heart Failure / Q000201:enzymology* / Q000209:etiology; D006352:Heart Ventricles; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis; D008264:Macrophages / Q000201:enzymology; D051379:Mice; D008942:Mitoxantrone / Q000009:adverse effects; D009136:Muscular Dystrophies / Q000201:enzymology; D017202:Myocardial Ischemia / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D012016:Reference Values; D018805:Sepsis / Q000201:enzymology / Q000378:metabolism
D007527:Isoenzymes; D008942:Mitoxantrone; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP