Role of oxidative stress on pathogenesis of hypertensive cerebrovascular lesions.
The hypertensive rat brain exhibited softening, severe edema and intracerebral hemorrhage. The NO(2) (-) + NO(3) (-) (NOx) level in the hypertensive rat brain was higher than in the normotensive rat brain. Light microscopy demonstrated severe arterial and arteriolar lesions with fibrinoid deposits and medial lesion. After injecting hypertensive rats with nitroblue tetrazolium (NBT), formazan deposits, which are the reaction product of reduction of NBT by superoxide, were observed in the microvessels and nervous tissue around the microvessels of injured brain. Immunohistochemistry showed that copper zinc superoxide dismutase and manganese superoxide dismutase expression of the endothelial cells of hypertensive rats were also upregulated in comparison with normotensive rat endothelial cells. Inducible nitric oxide synthase and endothelial nitric oxide synthase expression in endothelial cells of normotensive rats were strongly positive, whereas the expression in hypertensive rat endothelial cells was weaker. Nitrotyrosine, a biomarker of peroxynitrite, which is a powerful oxidant formed by the reaction of nitric oxide (NO) with superoxide, was found in the microvessels, injured arteries and arterioles and infarcted brain tissue. Deposition of a major aldehydic product of lipid peroxidation, that is, 4-hydroxy-2-nonenal (4-HNE) was found in microvessels, perivascular tissue, and edematous and infarcted brain. Hypertensive cerebrovascular disease is the result of hypertension-induced oxidative stress.
Suzuki
Keiji
K
Geriatrics Research Institute, Faculty of Medicine, Gunma University, Maebashi, Gunma 371-0847, Japan. kusakabe@health.gunma-u.ac.jp
Nakazato
Kyoumi
K
Kusakabe
Takahiko
T
Nagamine
Takeaki
T
Sakurai
Hiromu
H
Takatama
Masamitu
M
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001160:Arterioles / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D020765:Intracranial Arterial Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D015854:Up-Regulation
D000447:Aldehydes; D009580:Nitroblue Tetrazolium; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; D013482:Superoxide Dismutase; C027576:4-hydroxy-2-nonenal