Effects of hypertension and FAAH inhibitor treatment of rats with primary and secondary hypertension considering the physicochemical properties of erythrocytes

Abstract

Hypertension is one of the most common cardiovascular diseases in the world and is associated with oxidative stress. The aim of this study was to examine the effect of the chronic administration of the fatty-acid amide hydrolase inhibitor (URB597-[3-(3-carbamoylphenyl)phenyl]N-cyclohexylcarbamate) to rats with primary (SHRs – spontaneously hypertensive rats) and secondary (DOCA-salt – 11-desoxycorticosterone acetate-salt-induced hypertension) hypertension on the composition and physicochemical properties of erythrocytes membrane. Because changes in membrane composition lead to modifications of electrical charge what may affect cell functions, the levels of following components were determined: four classes of membrane phospholipids (by HPLC – high-performance liquid chromatograph), sialic acid (by resorcinol method), lipid peroxidation product – malondialdehyde (by GCMS – gas chromatography-mass spectrometry). The reduced levels of phospholipids and sialic acid, as well as the increased levels of malonodialdehyde observed in the erythrocyte membrane of rats with primary and secondary hypertension led to a decrease in the negative electrical charge of the membrane. Long-term administration of URB597 to SHRs and DOCA-salt-treated rats partially prevented changes caused by hypertension. Using theoretical equations and the dependence of cell surface charge density as a function of pH, total surface concentrations of acid and base groups and their association constants have been determined. Considering the changes in physicochemical parameters of erythrocyte membranes, URB597 can be considered a potential protective factor for erythrocytes in situations of metabolic changes associated with oxidative stress.

Keywords:

• Hypertension
• URB597electrical properties
• membrane composition
• erythrocyte

Compliance with ethical standards

All applicable national and institutional guidelines for the care and use of animals were followed. All procedures and experimental protocols were approved by the local Animal Ethics Committee in Białystok (Poland).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This publication has received financial support from the Polish Ministry of Science and Higher Education under subsidy for maintaining the research potential of the Faculty of Biological and Chemical, University of Bialystok. Zetasizer Nano ZS was funded by the European Funds for Regional Development and the National Funds of Ministry of Science and Higher Education, as part of the Operational Program Development of Eastern Poland 2007–2013, project: POPW.01.03.00-20-044/11.