Lipid peroxidation and nitric oxide inactivation in postmenopausal women

Abstract

Original ArticleCardiovascular diseases are less prevalent in premenopausal women and in those receiving hormone replacement therapy as compared with postmenopausal women and men 1 . This protective effect is attributed to estrogens, and one of the mechanisms of action may be related to the metabolism of plasma lipoproteins 2 .Estrogens reduce LDL-cholesterol and increase HDLcholesterol 3 . However, these changes in lipid profile only contribute to approximately 25% of the protective effect of estrogens 4 . Other potential mechanisms of action of estrogens may include protection against LDL oxidation 5 , reduction in lipoprotein(a), potentiation of fibrinolysis 6 , and increase in insulin sensitivity. In the arteries, estrogens improve vasodilating function, decrease calcification, secretion of cell adhesion molecules (E-selectin, ICAM-1, and VCAM-1), and formation of atherosclerotic lesions 7 .Direct action of estrogens on the arterial wall has also been demonstrated. The administration of estrogens for prolonged periods inhibits the deposition of cholesterol in the arteries and thickening of the intima in monkeys and rabbits fed an atherogenic diet 8 . However, the mechanisms determining the direct effects of estrogens on the arterial wall have not been completely elucidated. The hemodynamic effects may be partially measured by the activity of estrogens on the synthesis of endothelial nitric oxide 9 . Estrogens have been suggested to possibly improve endothelial function and decrease the risks of atherosclerosis in premenopausal women. Nitric oxide has its bioactivity reduced in postmenopausal women. However, it is not clear whether this occurs due to its lower production by nitric oxide synthase, or whether nitric oxide is inactivated by reaction with the superoxide radical also generated by endothelial cells, forming the peroxynitrite anion (ONOO -), which is a strong oxidizing agent.Peroxynitrite is decomposed into other reactive oxygen species ( fig. 1) 10 and reacts with tyrosine residues of proteins to form nitrotyrosine 11 . Although little is known NOx, nitrotyrosine, COx, CE 18:2 -OOH, and PC-OOH were higher in the postmenopausal period (33.8±22.3 µM; 230±130 nM; 55±19 ng/µL; 17±8.7 nM; 2775±460 nM, respectively) Objective -To assess the effect of endogenous estrogens on the bioavailability of nitric oxide (·NO) and in the formation of lipid peroxidation products in pre-and postmenopausal women. Methods -NOx and S-nitrosothiols were determined by gaseous phase chemiluminescence, nitrotyrosine was determined by ELISA, COx (cholesterol oxides) by gas chromatography, and cholesteryl linoleate hydroperoxides (CE 18:2 -OOH), trilinolein (TG 18:2 -OOH), and phospholipids (PC-OOH) by HPLC in samples of plasma. Results -The concentrations of

Mental stress induces sustained elevation of blood pressure and lipid peroxidation in postmenopausal women

“…5). This basal NOx finding is consistent with the results of some recent studies (Nawate et al, 2005;Pereira et al, 2003). However, there are contradictory results regarding the effects of estrogen replacement on plasma NOx levels in postmenopausal women (Cagnacci et al, 2003;Khorram et al, 2002;Konukoglu et al, 2000).…”

Estrogen is a modulator of vascular inflammation

“…One of the factors compromising estrogen effects in aging might be an increased oxidative stress in the vascular tissue. A study by Pereira et al has demonstrated an increase in proinflammatory nitrotyrosine levels in plasma following menopause (46). Similar changes in the vascular tissue may adversely affect the nongenomic protective pathways elicited through ERa, with a loss of estrogen-mediated beneficial effects on the vasculature (47).…”

Postprandial lipid oxidation and cardiovascular disease risk

“…The lower production of NO was related to either reduced availability of NO synthase or inactivation of NO by the reaction of superoxide radical forming the peroxynitrite (ONOO -), which is a strong oxidizing agent. The peroxynitrite and its decomposition products induce peroxidation of the membrane lipids, causing endothelial lesions and an increase in vascular permeability [39]. Kanazawa et al [40] demonstrated that dietary LOOH generated alkylperoxyl radical (LOO -) after its reaction with various heme compounds such as myoglobin, cytochrome c, hemin, and hematin.…”