The developmental profile of certain enzymatic antioxidants as well as the generation of reactive oxygen species was studied in the rat cerebral microvessels during first three weeks of life and the levels were compared to those present in adults. The data showed a higher generation of superoxide anion (+67%) and H2O2 (+200%) at postnatal day (PND) 21. Superoxide anion production was significantly lower (-24%) at PND 14 and almost comparable to adult values at PND 7. The activity of superoxide dismutase increased with development and attained an adult level at PND 21. Catalase was higher in neonates with a maximum activity at PND 7 and 14 (+68, 69%). The measurement of microvessel glutathione and glutathione-related antioxidant enzymes showed that glutathione level was higher at PND 7, which declined to an adult level at PND 14. Se-dependent GPx showed a marked increase between PND 14 and 21, however, it declined in adults. The activity of Se-independent glutathione peroxidase was very low in cerebral microvessels. Glutathione reductase activity in 7-day-old, that was comparable to adult level, declined at PND 14 and 21. The level of glutathione S-transferase was higher (+43%) at PND 21. The activity of microvessel marker enzyme gamma-glutatmyl transpeptidase increased with age, whereas, alkaline phosphatase showed a slight increase up to PND 14 and thereafter it declined. Lipid peroxidation was found to be significantly lower (-18%) at PND 21 as compared to adults. It may be concluded that developing cerebral microvessels contain high levels of several antioxidant enzymes that are more or equal to those present in adult brain microvessels. 相似文献
We investigated whether abnormal pteridine metabolism is related to coronary endothelial dysfunction in insulin-resistant subjects.
BACKGROUND
Depletion of tetrahydrobiopterin (BH4) and elevation of the 7,8-dihydrobiopterin (BH2) (activating and inactivating cofactors of nitric oxide synthase [NOS], respectively) contribute to impairment of NO-dependent vasodilation through reduction of NOS activity as well as increased superoxide anion generation in insulin-resistant rats.
METHODS
Thirty-six consecutive nondiabetic, normotensive and nonobese subjects with angiographically normal coronary vessels were studied. Traditional coronary risk factors, plasma pteridine levels, activities of erythrocyte dihydropteridine reductase (DHPR), the recycling enzyme that converts BH2 to BH4 and lipid peroxide (LPO) levels were measured and coronary endothelial function was assessed with graded infusions of acetylcholine (ACh).
RESULTS
When we divided patients into tertiles based on insulin sensitivity, we observed stepwise decreases in the maximal ACh-induced vasodilation and plasma BH4/7,8-BH2 ratio, and increases in coronary LPO production as insulin sensitivity decreased. The ACh-induced vasodilation was positively correlated with insulin sensitivity, BH4/7,8-BH2 ratio and DHPR activity. Furthermore, BH4/7,8-BH2 was inversely correlated with DHPR activity and insulin sensitivity. In multiple stepwise regression analysis, BH4/BH2 was independently related to ACh-induced vasodilation and accounted for 39% of the variance. However, no significant correlation existed between other traditional risk factors and BH4/7,8-BH2.
CONCLUSIONS
These results indicate that both abnormal pteridine metabolism and vascular oxidative stress are linked to coronary endothelial dysfunction in the insulin-resistant subjects. 相似文献