The Role of Oxidative Stress on Pathogenesis of Hypertensive Arterial Lesions in Rat Mesenteric Arteries.

Abstract

Examination of the mesenteric arteries of experimental hypertensive rats revealed leukocyte adhesion to the endothelium, leukocyte infiltration, deposition of fibrinoid substance in the intima, and severe medial smooth muscle cell injury. After injecting hypertensive rats with nitroblue tetrazolium (NBT), formazan deposits which were reaction product that NBT was reduced by superoxide were observed in the endothelial and medial cells of uninjured arteries. Formazan deposition was observed in neutrophils in the lumen of the injured arteries, neutrophils adhering to their endothelium, and neutrophils that had infiltrated in the intima and media. Marked upregulation copper zinc superoxide dismutase (CuZnSOD) and manganese superoxide dismutase (MnSOD) expression was found in the endothelial cells of the arteries of hypertensive rats. Endothelial expression of inducible nitric oxide synthase (iNOS: NOS II) and endothelial nitric oxide synthase (eNOS: NOS III) was strong in the arteries of normotensive rats and decreased in the injured arteries of hypertensive rats, but slight iNOS upregulation was found in the endothelium of uninjured arteries. Deposition of 4-hydroxy-2-nonenal (4-HNE) was observed in the intima of the injured arteries of hypertensive rats. Conclusion: Hypertensive arterial disease is the result of hypertension-induced oxidative stress produced by neutrophils, endothelial cells, and medial smooth muscle cells as well as enzyme activity release by neutrophils activated by hypertension.