DIFFERENTIAL DISTRIBUTION OF ECNOS AND INOS MESSENGER-RNA IN RAT-HEART AFTER ENDOTOXIN ADMINISTRATION

To evaluate the relationship between cardiovascular injury and the pat hological significance of endothelial constitutive nitric oxide syntha se (ecNOS) and inducible nitric oxide synthase (iNOS) in endotoxic sho ck, Wistar rats were injected intraperitoneally with 10 mg/kg Escheric hia coli endotoxin and the resulting cardiovascular changes observed u sing immunohistochemistry, immunoelectron microscopy, the reverse tran scription polymerase chain reaction (RT-PCR) and in situ hybridization at 4, 6, 8 and 10 h after endotoxin administration. Immunohistochemic al and electron microscopic observations showed that ecNOS was localiz ed in the cytoplasmic vesicles and rough endoplasmic reticulum of the endothelium of coronary arteries and intermyocardial capillaries in bo th control and endotoxin-treated rats. iNOS was localized in the cytop lasmic vesicles and endoplasmic reticulum of vascular endothelial cell s, vascular smooth muscle cells and cardiomyocytes after endotoxin adm inistration. The RT-PCR study confirmed the expression of ecNOS and iN OS mRNA in the heart tissues of all animals including controls. lit si tu hybridization showed that ecNOS mRNA was expressed in the cytoplasm of vascular endothelial cells in control and endotoxin-treated rats. After endotoxin administration, iNOS mRNA was strongly expressed in va scular endothelial cells, vascular smooth muscle cells, cardiomyocytes and a small number of macrophages. Bacterial lipopoly-saccharide indu ces rapid release of nitric oxide in the microvasculature and cardiomy ocytes resulting in the depression of cardiomyocyte contraction. These findings may describe the cardiac response after endotoxin treatment.