Nitric oxide, cholesterol oxides and endothelium-dependent vasodilation in plasma of patients with essential hypertension

Author(s)

P. Moriel ^[1] ; A. Sevanian ^[2] ; S. Ajzen ^[3] ; M.T. Zanella ^[4] ; F.L. Plavnik ^[5] ; H. Rubbo ^[6] ; D.S.P. Abdalla ^[7]

Affiliation

^[1] Universidade de São Paulo. Faculdade de Ciências Farmacêuticas. Departamento de Análises Clínicas e Toxicológicas - Brasil

^[2] University of Southern California. School of Pharmacy. Department of Toxicology - Estados Unidos

^[3] Universidade Federal de São Paulo. Departamentos de Endocrinologia e Nefrologia - Brasil

^[4] Universidade Federal de São Paulo. Departamentos de Endocrinologia e Nefrologia - Brasil

^[5] Universidade Federal de São Paulo. Departamentos de Endocrinologia e Nefrologia - Brasil

^[6] Universidad de la Republica. Departamento de Bioquimica - Uruguai

^[7] Universidade de São Paulo. Faculdade de Ciências Farmacêuticas. Departamento de Análises Clínicas e Toxicológicas - Brasil

• Document type: Journal article
• Source: Brazilian Journal of Medical and Biological Research; v. 35, n. 11, p. 1301-1309, 2002-11-00.

Abstract

The objective of the present study was to identify disturbances of nitric oxide radical (·NO) metabolism and the formation of cholesterol oxidation products in human essential hypertension. The concentrations of·NO derivatives (nitrite, nitrate, S-nitrosothiols and nitrotyrosine), water and lipid-soluble antioxidants and cholesterol oxides were measured in plasma of 11 patients with mild essential hypertension (H: 57.8 ± 9.7 years; blood pressure, 148.3 ± 24.8/90.8 ± 10.2 mmHg) and in 11 healthy subjects (N: 48.4 ± 7.0 years; blood pressure, 119.4 ± 9.4/75.0 ± 8.0 mmHg).Nitrite, nitrate and S-nitrosothiols were measured by chemiluminescence and nitrotyrosine was determined by ELISA. Antioxidants were determined by reverse-phase HPLC and cholesterol oxides by gas chromatography. Hypertensive patients had reduced endothelium-dependent vasodilation in response to reactive hyperemia (H: 9.3 and N: 15.1% increase of diameter 90 s after hyperemia), and lower levels of ascorbate (H: 29.2 ± 26.0, N: 54.2 ± 24.9 µM), urate (H: 108.5 ± 18.9, N: 156.4 ± 26.3 µM), ß-carotene (H: 1.1 ± 0.8, N: 2.5 ± 1.2 nmol/mg cholesterol), and lycopene (H: 0.4 ± 0.2, N: 0.7 ± 0.2 nmol/mg cholesterol), in plasma, compared to normotensive subjects. The content of 7-ketocholesterol, 5alpha-cholestane-3ß,5,6ß-triol and 5,6alpha-epoxy-5alpha-cholestan-3alpha-ol in LDL, and the concentration of endothelin-1 (H: 0.9 ± 0.2, N: 0.7 ± 0.1 ng/ml) in plasma were increased in hypertensive patients. No differences were found for ·NO derivatives between groups. These data suggest that an increase in cholesterol oxidation is associated with endothelium dysfunction in essential hypertension and oxidative stress, although ·NO metabolite levels in plasma are not modified in the presence of elevated cholesterol oxides. (AU)

• FAPESP's process: 97/05090-3 - Possible connections between hypertension and hypercholesterolemia in relation to arteriosclerosis: inactivation paths of nitric oxide and oxidation of lipoproteins
• Grantee: Dulcineia Saes Parra Abdalla
• Support Opportunities: Research Projects - Thematic Grants