INDUCIBLE NITRIC-OXIDE SYNTHASE GENE-TRANSCRIPTION AND PROTEIN-ACTIVITY IN THE RAT-HEART DURING ENDOTOXEMIA

Septicaemia leads to an impairment of myocardial contractility in anim als and humans. Cytokines released during endotoxaemia are capable of increasing inducible nitric oxide synthase (iNOS) expression in vitro in myocytes, endothelial cells and macrophages. The aim of this study was to assess whether iNOS gene transcription occurs in the myocyte in vivo. Rats were injected with intraperitoneal endotoxin, Myocardial s ections obtained 4, 6 and 8 hours after infection were hybridised with oligonucleotides complementary to iNOS cDNA. Myocardial homogenates w ere used to measure NOS enzyme activity and to detect iNOS mRNA. Uninf ected control animals did not demonstrate myocardial iNOS expression. Myocardium from endotoxaemic animals contained iNOS mRNA and high calc ium-independent NOS enzyme activity, In situ hybridisation did not loc alise iNOS to myocytes but to cells located between myocytes. Endotoxa emia leads to iNOS gene transcription and calcium-independent NOS enzy me activity in the rat myocardium. In situ hybridisation demonstrates that iNOS is not transcribed by the myocyte in vivo. (C) 1997 Academic Press.