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 prolonged release of large amounts of NO which may be cytotoxic and/or inhibit myocyte contractility. It has been suggested that this mechanism specifically contributes to heart failure caused by dilated cardiomyopathy (DCM). To test this hypothesis we compared the myocardial amount and localization of iNOS in myocardial biopsies from patients with heart failure caused by either DCM or ischemic heart disease (IHD). During heart transplantation, myocardial biopsies collected from the diseased heart after explantation were frozen in liquid nitrogen. Twenty-two patients in NYHA class III-IV were included (DCM: n = 8; IHD: n = 14). In each biopsy, iNOS expression was assessed using reverse transcription polymerase chain reaction (RT-PCR), and visualized by immunohistochemistry. iNOS was detected in all biopsies. Intriguingly, the amount of iNOS mRNA (shown as iNOS cDNA normalized to GADPH cDNA) did not differ significantly between the two groups (DCM 30 +/- 7; IHD 20 +/- 6, mean +/- S.E.M., P > 0.05). Similarly, no inter-group differences in the amount of iNOS protein (Western) were observed. iNOS was invariably located to vascular endothelial and smooth muscle cells. In addition, an iNOS reaction in relation to the myocyte membrane was found in 4 of the 22 patients. These four patients (two from each group) had significantly (P < 0.05) higher iNOS/GADPH ratios (54 +/- 20) than patients without 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 IHD. iNOS is located primarily and invariably in the endothelium and vascular smooth muscle cells of the myocardial vasculature and its expression appears to be associated with the condition of heart failure per se rather than related to the heart failure etiology.