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Electrolyte and transporter responses to angiotensin II induced hypertension in female and male rats and mice.
Acta Physiologica ( IF 5.6 ) Pub Date : 2020-02-12 , DOI: 10.1111/apha.13448
Luciana C Veiras 1, 2 , Brandon E McFarlin 1 , Donna L Ralph 1 , Vadym Buncha 3 , Jessica Prescott 1 , Borna S Shirvani 1 , Jillian C McDonough 1 , Darren Ha 1 , Jorge Giani 2 , Susan B Gurley 4 , Mykola Mamenko 3 , Alicia A McDonough 1
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AIM Sexual dimorphisms are evident along the nephron: Females (F) exhibit higher ratios of renal distal to proximal Na+ transporters' abundance, greater lithium clearance (CLi ) more rapid natriuresis in response to saline infusion and lower plasma [K+ ] vs. males (M). During angiotensin II infusion hypertension (AngII-HTN) M exhibit distal Na+ transporter activation, lower proximal and medullary loop transporters, blunted natriuresis in response to saline load, and reduced plasma [K+ ]. This study aimed to determine whether responses of F to AngII-HTN mimicked those in M or were impacted by sexual dimorphisms evident at baseline. METHODS Sprague Dawley rats and C57BL/6 mice were AngII infused via osmotic minipumps 2 and 3 weeks, respectively, and assessed by metabolic cage collections, tail-cuff sphygmomanometer, semi-quantitative immunoblotting of kidney and patch-clamp electrophysiology. RESULTS In F rats, AngII-infusion increased BP to 190 mm Hg, increased phosphorylation of cortical NKCC2, NCC and cleavage of ENaC two to threefold, increased ENaC channel activity threefold and aldosterone 10-fold. K+ excretion increased and plasma [K+ ] decreased. Evidence of natriuresis in F included increased urine Na+ excretion and CLi , and decreased medullary NHE3, NKCC2 and Na,K-ATPase abundance. In C57BL/6 mice, AngII-HTN increased abundance of distal Na+ transporters, suppressed proximal-medullary transporters and reduced plasma [K+ ] in both F and M. CONCLUSION Despite baseline sexual dimorphisms, AngII-HTN provokes similar increases in BP, aldosterone, distal transporters, ENaC channel activation and K+ loss accompanied by similar suppression of proximal and loop Na+ transporters, natriuresis and diuresis in females and males.

中文翻译:

电解质和转运蛋白对血管紧张素II诱导的雌性和雄性大鼠和小鼠高血压的反应。

目的:肾脏周围有明显的两性分化:女性(F)相对于男性输注盐水和降低血浆[K +]表现出较高的肾脏远端Na +和近端Na +转运蛋白丰度比值,更大的锂清除率(CLi)更快地利尿。 M)。在血管紧张素II输注高血压(AngII-HTN)期间,M表现出远端Na +转运蛋白激活,较低的近端和髓样环转运蛋白,响应于盐分负荷的钠尿钝化和血浆[K +]降低。这项研究旨在确定F对AngII-HTN的反应是否模仿M中的反应,还是受到基线明显的性二态影响。方法分别将Sprague Dawley大鼠和C57BL / 6小鼠通过渗透微型泵分别输注AngII 2周和3周,并通过代谢笼收集,尾袖血压计进行评估,肾脏的半定量免疫印迹和膜片钳电生理学。结果在F大鼠中,AngII输注使BP增加到190 mm Hg,皮质NKCC2,NCC的磷酸化增加,ENaC的裂解增加2到3倍,ENaC通道活性增加3倍,醛固酮增加10倍。K +排泄增加,血浆[K +]减少。F中钠尿的证据包括尿液Na +排泄和CLi增加,髓质NHE3,NKCC2和Na,K-ATPase丰度降低。在C57BL / 6小鼠中,AngII-HTN增加了F和M中远端Na +转运蛋白的含量,抑制了近端髓质转运蛋白的含量,并降低了血浆[K +]。结论尽管基线存在性别差异,AngII-HTN引起了BP,醛固酮,远端运输器
更新日期:2020-02-12
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