Acceleration of hypertensive cerebral injury by the inhibition of xanthine-xanthine oxidase system in stroke-prone spontaneously hypertensive rats.
It is well-known that, in ischemic cerebral injury, a free radical and its byproducts are generated by xanthine-xanthine oxidase system and eliminated by scavengers such as superoxide dismutase (SOD), catalase, uric acid and ascorbic acid. To investigate the possible involvement of the xanthine-xanthine oxidase system in hypertensive cerebral injury, we examined chronological changes in uric acid level in the cerebral cortex and the effects of the inhibition of xanthine oxidase or catalase using stroke-prone spontaneously hypertensive rats (SHRSP). In young SHRSP, uric acid content was lower than age-matched Wistar-Kyoto rats (WKY), but in mature SHRSP strongly exposed to oxidative stress uric acid content had risen dramatically. Administration of allopurinol, an inhibitor of xanthine oxidase, caused a marked decrease in uric acid content. In these SHRSP, cerebral injury was much more intense compared to the control group. On the other hand, administration of aminotriazole, an inhibitor of catalase, did not affect the brain pathology of SHRSP, in spite of a mild reduction in tissue uric acid content. These results suggest that the xanthine-xanthine oxidase system is not the major source of free radical generation in hypertensive cerebral injury. Moreover, the results also suggest that tissue uric acid may have a key role for the incidence of hypertensive cerebral injury in SHRSP.
Maenishi
O
O
Department of Pathology, Kinki University School of Medicine, Osaka, Japan.
Ito
H
H
Suzuki
T
T
D000493:Allopurinol / Q000494:pharmacology; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000473:pathology*; D002374:Catalase / Q000037:antagonists & inhibitors; D002540:Cerebral Cortex / Q000378:metabolism; D002561:Cerebrovascular Disorders / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020022:Genetic Predisposition to Disease; D006973:Hypertension / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics*; D011921:Rats, Inbred WKY; D014527:Uric Acid / Q000378:metabolism; D019820:Xanthine; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*; D014970:Xanthines / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D014970:Xanthines; D019820:Xanthine; D014527:Uric Acid; D000493:Allopurinol; D002374:Catalase; D014969:Xanthine Oxidase; D000640:Amitrole