The Sry3 Y Chromosome Locus Elevates Blood Pressure and Renin-Angiotensin System Indexes

The Sry3 Y Chromosome Locus Elevates Blood Pressure and Renin-Angiotensin System Indexes
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DOI:
10.1016/j.genm.2010.11.014
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发表时间:
2011-04-01
期刊:
影响因子:
--
通讯作者:
Milsted, Amy
Milsted, Amy
中科院分区:
其他
文献类型:
--
作者:
Ely, Daniel;Boehme, Shannon;Milsted, Amy

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背景:性别决定区Y(Sry)是一种转录因子。我们的研究小组已经表明,在Wistar-Kyoto(WKY)和自发性高血压(SHR)大鼠中存在多个Sry拷贝,并且它们具有与睾丸决定无关的新功能。目的:我们假设,基于先前的体外研究,将外源性Sry 3递送到血压正常的WKY雄性肾脏将激活肾素-血管紧张素系统(RAS)并升高血压(BP)。将Sry 3或对照载体电穿孔至雄性WKY大鼠的左肾,并进行以下测量:通过遥测法测量血压,通过放射免疫测定法测量肾素-血管紧张素,通过HPLC结合电化学检测法测量血浆和组织中的儿茶酚胺,通过火焰光度法测量钠,通过ELISA测量菊粉。与对照组相比,Sry 3使血压升高10 - 20 mm Hg(P < 0.01),并使尿钠水平显著降低40%(P < 0.05)。Sry 3使肾脏血管紧张素II和血浆肾素活性增加> 100%(P < 0.01和P < 0.05)。结论:本研究证实并扩展了Sry 3是SHR高血压Y染色体表型的基因之一的论点,并与Sry 3引起的组织RAS活性增加和钠重吸收增加相一致。(Gend 2011;8:126-138)由Elsevier HS Journals,Inc.
Background: Sex-determining region Y (Sry) is a transcription factor. Our research group has shown that there are multiple copies of Sry in Wistar-Kyoto (WKY) and spontaneous hypertensive (SHR) rats, and that they have novel functions separate from testes determination.Objective: We hypothesized that exogenously delivered Sry3 to the normotensive WKY male kidney would activate the renin-angiotensin system (RAS) and raise blood pressure (BP), based on previous in vitro studies.Methods: Sry3 or control vector was electroporated to the left kidney of male WKY rats and the following measurements were taken: BP by telemetry, renin-angiotensin measures by radioimmunoassay, plasma and tissue catecholamines by HPLC with electrochemical detection, sodium by flame photometry, and inulin by ELISA.Results: Sry3 increased BP 10 to 20 mm Hg compared with controls (P < 0.01) and produced a significant 40% decrease in urine sodium compared with controls (P < 0.05). Sry3 increased renal angiotensin II and plasma renin activity by > 100% compared with controls (P < 0.01 and P < 0.05, respectively).Conclusion: The findings presented here confirm and extend the argument for Sry3 as one of the genes responsible for the SHR hypertensive Y chromosome phenotype and are consistent with increased tissue RAS activity due to Sry3 and increased sodium reabsorption. (Gend Med. 2011;8:126-138) Published by Elsevier HS Journals, Inc.