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

Effects of hypertension and FAAH inhibitor treatment of rats with primary and secondary hypertension considering the physicochemical properties of erythrocytes
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DOI:
10.1080/15376516.2020.1727595
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发表时间:
2020-02-20
影响因子:
3.2
通讯作者:
Skrzydlewskac,ElZbieta
Skrzydlewskac,ElZbieta
中科院分区:
医学4区
文献类型:
--
作者:
Dobrzynska,Izabela;Szachowicz-Petelska,Barbara;Skrzydlewskac,ElZbieta

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高血压是世界上最常见的心血管疾病之一,与氧化应激有关。本研究的目的是检查脂肪酸酰胺水解酶抑制剂(URB 597-[3-(3-氨基甲酰基苯基)苯基] N-环己基氨基甲酸酯)对原发性(SHR-自发性高血压大鼠)和继发性(DOCA-盐-11-脱氧皮质酮醋酸盐-盐诱导的高血压)高血压大鼠长期给药对红细胞膜组成和理化性质的影响。由于膜组成的变化导致可能影响细胞功能的电荷改变,因此测定了以下组分的水平:四类膜磷脂(通过HPLC -高效液相色谱法)、唾液酸(通过间苯二酚法)、脂质过氧化产物-丙二醛(通过GCMS -气相色谱-质谱法)。在原发性和继发性高血压大鼠红细胞膜中观察到的磷脂和唾液酸水平降低以及丙二醛水平升高导致膜负电荷减少。对SHR和DOCA盐处理的大鼠长期给予URB 597部分预防了高血压引起的变化。使用理论方程和细胞表面电荷密度的依赖性作为pH值的函数,总表面浓度的酸和碱的基团和它们的缔合常数已被确定。考虑到红细胞膜的理化参数的变化,URB 597可以被认为是在与氧化应激相关的代谢变化的情况下对红细胞的潜在保护因子。
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.