Cell damage and liberation of nitric oxide synthase in rat heart induced by endotoxin administration

To evaluate the relationship between cardiovascular injury and the pathological aspect of the liberation of the nitric oxide synthase in endotoxin shock, Wistar rats were injected intraperitoneally with 10 mg/kg E. coli endotoxin and the cardiovascular changes were observed chronologically by immunohistochemical and electron microscopic techniques at 2, 4, 8 and 12 h respectively after endotoxin administration. Light microscopically, irregular contraction of cardiomyocytes was observed in the early stage. After 8 h of endotoxin administration, occasional disintegration of the myocytes as well as lysis of myofibrils became prominent, and diminished stainings of myoglobin and actin were seen in these myocytes. Ultrastructurally, increased pinocytotic vesicles were observed in endothelial cells associated with widened intercellular spaces, and vacuolization of endothelial and medial cells of the vasculature. In cardiomyocytes, swelling of mitochondria and interstitial edema were noted at 12 h after endotoxin administration. Immunohistochemically, an increased permeability of albumin was noted in the myocytes and vasculature and nitric oxide synthase was localized on the cytomembrane of the endothelium of the coronary arteries in control rats. After endotoxin administration, the reaction products of nitric oxide synthase increased in the endothelial and medial cells, and cardiomyocytes. These results suggest that the increased activity of nitric oxide synthase is an important factor in the excessive production of nitric oxide and in promoting the pathologic changes in the cardiovascular system after endotoxin administration.