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卵巢切除术和高盐饮食会增加成年Wistar大鼠的血压,并改变其外周血单核细胞中的钠转运蛋白。

Ovariectomy and high salt increase blood pressure and alter sodium transport proteins in peripheral blood mononuclear cells of adult Wistar rats.

作者信息

Vlachovsky Sandra G, Di Ciano Luis A, Oddo Elisabet M, Azurmendi Pablo J, Goette Nora P, Arrizurieta Elvira E, Silberstein Claudia, Ibarra Fernando R

机构信息

Universidad de Buenos Aires, Laboratorio de Riñón Experimental y Bioquímica Molecular, Instituto de Investigaciones Médicas A. Lanari, Buenos Aires, Argentina.

Universidad de Buenos Aires, Laboratorio Hematología Investigación, Instituto de Investigaciones Médicas A. Lanari, Buenos Aires, Argentina.

出版信息

Exp Physiol. 2021 Oct;106(10):2107-2123. doi: 10.1113/EP089553. Epub 2021 Aug 17.

Abstract

NEW FINDINGS

What is the central question of this study? In a model of salt-sensitive hypertension in ovariectomized (oVx) adult Wistar rats, what is the expression of proteins related to sodium transport in peripheral blood mononuclear cells (PBMCs), and how does the response of proteins to high sodium intake compare with changes in blood pressure in intact female rats? What is the main finding and its importance? Sodium transport proteins in PBMCs react to high sodium and blood pressure markedly differently in oVx versus intact female rats. Protein expression shows sodium and pressure sensitivity. Renal immune cells increase in oVx under high salt.

ABSTRACT

Hypertension is a worldwide public health problem. High sodium consumption is associated with hypertension, and hypertensive mechanisms involve immunity cells. Peripheral blood mononuclear cells (PBMCs) are endowed with proteins related to sodium transport. We studied their abundance in PBMCs from intact (IF) or ovariectomized (oVx) adult Wistar rats under normal (NS) or high (HS) salt intake. Ovariectomy was performed at 60 days of life. At 145 days, one group of IF and oVx rats received NS or HS intake for 5 days. Another group of IF HS and oVx HS rats received hydralazine (HDZ) to reduce blood pressure (BP). Sodium balance and BP were recorded. Expression of Na ,K -ATPase (NKA), Na -K -2Cl cotransporter 1 (NKCC1), serum/glucocorticoid-regulated kinase 1 (SGK1), dopamine D1 like receptor (D1DR), CD4 and CD8 were determined in PBMCs and CD45 leukocytes in renal tissue. IF HS rats showed increased natriuresis and normal BP. NKA and CD4 expression diminished in IF HS. Instead, oVx HS rats had sodium retention and high BP and increased the expression of NKA, NKCC1, D1DR, CD4 and CD8 in PBMCs. Renal CD45 leukocytes increased in oVx HS rats. HDZ decreased BP in all rats. Upon HDZ treatment, NKA did not change, NKCC1 decreased in oVx HS rats, while SGK1 increased in both IF HS and oVx HS rats. Hormonal background determines BP response and the expression of proteins related to sodium transport in PBMCs and renal immune cells at HS intake. The analysis of NKA, NKCC1 and SGK1 expression in PBMCs differentiated salt-sensitivity from BP variations.

摘要

新发现

本研究的核心问题是什么?在去卵巢(oVx)成年Wistar大鼠的盐敏感性高血压模型中,外周血单核细胞(PBMC)中与钠转运相关的蛋白质表达情况如何,以及这些蛋白质对高钠摄入的反应与完整雌性大鼠的血压变化相比如何?主要发现及其重要性是什么?在oVx大鼠与完整雌性大鼠中,PBMC中的钠转运蛋白对高钠和血压的反应明显不同。蛋白质表达显示出钠敏感性和压力敏感性。在高盐条件下,oVx大鼠的肾免疫细胞增加。

摘要

高血压是一个全球性的公共卫生问题。高钠摄入与高血压相关,且高血压机制涉及免疫细胞。外周血单核细胞(PBMC)具有与钠转运相关的蛋白质。我们研究了正常(NS)或高(HS)盐摄入条件下,来自完整(IF)或去卵巢(oVx)成年Wistar大鼠的PBMC中这些蛋白质的丰度。在60日龄时进行卵巢切除术。在145日龄时,一组IF和oVx大鼠接受NS或HS摄入5天。另一组IF HS和oVx HS大鼠接受肼屈嗪(HDZ)以降低血压(BP)。记录钠平衡和血压。测定PBMC以及肾组织中CD45白细胞中Na⁺,K⁺-ATP酶(NKA)、Na⁺-K⁺-2Cl协同转运蛋白1(NKCC1)、血清/糖皮质激素调节激酶1(SGK1)、多巴胺D1样受体(D1DR)、CD4和CD8的表达。IF HS大鼠表现出利钠增加且血压正常。IF HS大鼠中NKA和CD4表达降低。相反,oVx HS大鼠出现钠潴留和高血压,且PBMC中NKA、NKCC1、D1DR、CD4和CD8的表达增加。oVx HS大鼠的肾CD45白细胞增加。HDZ使所有大鼠的血压降低。HDZ治疗后,NKA无变化,oVx HS大鼠的NKCC1降低,而IF HS和oVx HS大鼠中的SGK1均增加。激素背景决定了高盐摄入时血压反应以及PBMC和肾免疫细胞中与钠转运相关蛋白质的表达。对PBMC中NKA、NKCC1和SGK1表达的分析区分了盐敏感性与血压变化。

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