Delivery of sry1, but not sry2, to the kidney increases blood pressure and sns indices in normotensive wky rats

Delivery of sry1, but not sry2, to the kidney increases blood pressure and sns indices in normotensive wky rats
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DOI:
10.1186/1472-6793-9-10
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发表时间:
2009-06-05
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影响因子:
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通讯作者:
Turner, Monte
Turner, Monte
中科院分区:
其他
文献类型:
--
作者:
Ely, Daniel;Milsted, Amy;Turner, Monte

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背景资料:我们的实验室已经表明,SHR Y染色体上的一个位点增加了SHR大鼠和具有SHR Y染色体的WKY大鼠(SHR/y大鼠)的血压(BP)。这个Y染色体高血压基因座的候选者是Sry,一种编码负责睾丸决定的转录因子的基因。SHR Y染色体上有6个不同的Sry基因座。以下研究检查了外源性Sry 1或Sry 2递送至肾脏是否会在28天内升高肾酪氨酸羟化酶、肾儿茶酚胺、血浆儿茶酚胺和遥测血压。我们通过电穿孔将50 μ g表达构建体Sry 1/pcDNA 3.1、Sry 2/pcDNA 3.1或对照载体递送到血压正常的WKY大鼠的左肾髓质中。每周进行空气应激以确定BP反应性。使用α肾上腺素能受体阻滞剂检测各组动物的肾功能和血浆激素模式以及药物干预。从Sry 1电穿孔和对照载体雄性动物中采集术前基线和每周血样,用于血浆肾素、醛固酮和皮质酮。结果:在接受Sry 1质粒的动物中,与对照组相比,21天后静息血浆去甲肾上腺素(NE,27%)和肾酪氨酸羟化酶含量(41%,p <0.05)显著增加。在2-4周之间,与对照组(125 mmHg)相比,用Sry 1电穿孔的动物(143 mmHg,p <0.05)的BP更高。同样,与对照组(28 mmHg,p < .001)相比,电穿孔Sry 1(41 mmHg)的雄性动物对空气应激的升压反应显著升高。Sry 2未升高BP或SNS指数,未进行进一步检查。在28天的时间内,电穿孔Sry 1和对照载体雄性之间的血浆肾素、醛固酮和皮质酮的激素谱没有显示出显著差异。α肾上腺素能受体阻断剂阻止了两种品系的空气应激升压反应。尿多巴胺显着增加后7天后Sry electroportion.Conclusion:这些结果是一致的作用Sry 1在增加血压直接或间接激活肾交感神经系统的活动。
Background: Our laboratory has shown that a locus on the SHR Y chromosome increases blood pressure (BP) in the SHR rat and in WKY rats with the SHR Y chromosome (SHR/y rat). A candidate for this Y chromosome hypertension locus is Sry, a gene that encodes a transcription factor responsible for testes determination. The SHR Y chromosome has six divergent Sry loci. The following study examined if exogenous Sry1 or Sry2 delivered to the kidney would elevate renal tyrosine hydroxylase, renal catecholamines, plasma catecholamines and telemetered BP over a 28 day period. We delivered 50 mu g of either the expression construct Sry1/pcDNA 3.1, Sry2/pcDNA 3.1, or control vector into the medulla of the left kidney of normotensive WKY rats by electroporation. Weekly air stress was performed to determine BP responsiveness. Separate groups of animals were tested for renal function and plasma hormone patterns and pharmacological intervention using alpha adrenergic receptor blockade. Pre-surgery baseline and weekly blood samples were taken from Sry1 electroporated and control vector males for plasma renin, aldosterone, and corticosterone. BP was measured by telemetry and tyrosine hydroxylase and catecholamines by HPLC with electrochemical detection.Results: In the animals receiving the Sry1 plasmid there were significant increases after 21 days in resting plasma norepinephrine (NE, 27%) and renal tyrosine hydroxylase content (41%, p < .05) compared to controls. BP was higher in animals electroporated with Sry1 (143 mmHg, p < .05) compared to controls (125 mmHg) between 2-4 weeks. Also the pressor response to air stress was significantly elevated in males electroporated with Sry1 (41 mmHg) compared to controls (28 mmHg, p < .001). Sry2 did not elevate BP or SNS indices and further tests were not done. The hormone profiles for plasma renin, aldosterone, and corticosterone between electroporated Sry1 and control vector males showed no significant differences over the 28 day period. Alpha adrenergic receptor blockade prevented the air stress pressor response in both strains. Urinary dopamine significantly increased after 7 days post Sry electroporation.Conclusion: These results are consistent with a role for Sry1 in increasing BP by directly or indirectly activating renal sympathetic nervous system activity.