Possíveis conexões entre hipertensão e hipercolesterolemia, em relação à aterosclerose vias de inativação do óxido nítrico e oxidação das lipoproteínas

Author(s)

Patricia Moriel

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
• Defense date: 2001-04-10

Examining board members

Dulcineia Saes Parra Abdalla; Marcelo Chiara Bertolami; Joel Claudio Heimann; Maria Teresa Zanella; Roberto Zatz

• Advisor: Dulcineia Saes Parra Abdalla

Abstract

Endothelial dysfunction plays an important role in the pathogenesis of coronary artery disease. Plasma cholesterol particularly that associated to LDL, has been suggested to be an important risk factor in the development of cardiovascular disease. Moreover, LDL oxidation is a crucial event in the pathogenesis of atherosclerosis. By the other hand, a reduced bioactivity of endothelial nitric oxide (•NO) has been implicated in the pathogenesis of atherosclerosis. The reduction of •NO activity in hypercholesterolemia and in other metabolic disorders associated with atherogenesis appears to be multifuctorial. However, the alterations of •NO production in hypercholesterolemia and hypertension is still controversial. The purpose of this study was to examine the relationship of lipid peroxidation, antioxidants and nitric oxide bioavailability with the impairment of endothelium dependent vasodilation in hypercholesterolemic (HC) (n = 18), hypertensive (H) (n = 11), and normolipidemic normotensive subjects (N) (n = 11). Ascorbate, urate, α tocopherol lycopene and β-carotene, as well as, lipid hydroxy/hydroperoxides were determined by HPLC. Paraoxonase, isoprostanes and endothelin were determined by ELISA The kinetics of LDL oxidation was monitored by incubating LDL with Cu2+. Oxysterols were determined by CG. Mode B ultrasonography was used to measure the blood flow and diameter in response to reactive hyperemia of brachial artery. Nitrate and Snitrosothiols in plasma were determined by chemiluminescence elicited by reaction of with ozone in the •NO analyzer (NOA280, Sievers, Corp.). Nitrotyrosine concentrations in plasma, LDL and HDL were determined by a chemiluminescence competitive ELISA developed in our laboratory with polyclonal antibody. Plasma ascorbate, lipid soluble antioxidants, the lag time and the endothelium dependent relaxation were lower in H and HC than in N. Lidid hydroxy/hydroperoxides and endothelin were higher in hypertension and hypercholesterolemia. The levels of plasma nitrate, S-nitrosothiols, total cholesterol. apo B, LDL-nitrotyrosine and LDL-cholesterol were significantly higher in HC than in N subjects. LDL cholesterol was negatively correlated to the percentage of diameter increase in response to hyperemia. The lower levels of the lipid soluble antioxidants may be important for the impairment of endothelial dependent vasodilation in hypercholesterolemia and hypertension. ln conclusion, in hypertension and hypercholesterolemia the levels of oxidized lipids, antioxidants, •NO bioavailability, and endothelin may contribute to the impairment of endothelial function and endothelium dependent relaxation, which is crucial to the development of atherosclerosis. (AU)