INDUCIBLE NITRIC-OXIDE SYNTHASE (INOS) IN THE HUMAN HEART - EXPRESSION AND LOCALIZATION IN CONGESTIVE-HEART-FAILURE

The inducible nitric oxide (NO) synthase (iNOS or NOS2) generates a pr olonged release of large amounts of NO which may be cytotoxic and/or i nhibit myocyte contractility. It has been suggested that this mechanis m specifically contributes to heart failure caused by dilated cardiomy opathy (DCM). To test this hypothesis we compared the myocardial amoun t and localization of iNOS in myocardial biopsies from patients with h eart failure caused by either DCM or ischemic heart disease (IHD). Dur ing heart transplantation, myocardial biopsies collected from the dise ased heart after explantation were frozen in liquid nitrogen. Twenty-t wo patients in NYHA class III-IV were included (DCM: n=8; IHD: n=14), In each biopsy, iNOS expression was assessed using reverse transcripti on polymerase chain reaction (RT-PCR), and visualized by immunohistoch emistry. iNOS was detected in all biopsies, Intriguingly, the amount o f iNOS mRNA (shown as iNOS cDNA normalized to GADPH cDNA) did not diff er significantly between the two groups (DCM 30 +/- 7; IHD 20 +/- 6, m ean +/- S.E.M. P>0.05). Similarly, no inter-group differences in the a mount of iNOS protein (Western) were observed. iNOS was invariably loc ated to vascular endothelial and smooth muscle cells. In addition, an iNOS reaction in relation to the myocyte membrane was found in 4 of th e 22 patients. These four patients (two from each group) had significa ntly (P<0.05) higher iNOS/GADPH ratios (54 +/- 20) than patients witho ut myocyte membrane iNOS reaction (17 +/- 15). In conclusion, iNOS is expressed in the myocardium of all patients with heart failure caused by either DCM or LHD. iNOS is located primarily and invariably in the endothelium and vascular smooth muscle cells of the myocardial vascula ture and its expression appears to be associted with the condition of heart failure per se rather than related to the heart failure etiology . (C) 1998 Academic Press.