Ely Daniel, Milsted Amy, Bertram Jason, Ciotti Mat, Dunphy Gail, Turner Monte E
Department of Biology, University of Akron, Akron, OH 44325, USA.
BMC Cardiovasc Disord. 2007 Feb 26;7:6. doi: 10.1186/1471-2261-7-6.
Our laboratory has shown that a locus on the SHR Y chromosome increases blood pressure (BP) in the SHR rat and in WKY rats that had the SHR Y chromosome locus crossed into their genome (SHR/y rat). A potential candidate for this Y chromosome hypertension locus is Sry, a gene that encodes a transcription factor that is responsible for testes development and the Sry protein may affect other target genes.
The following study examined if exogenous Sry would elevate adrenal Th, adrenal catecholamines, plasma catecholamines and blood pressure. We delivered 10 mug of either the expression construct, Sry1/pcDNA 3.1, or control vector into the adrenal medulla of WKY rats by electroporation. Blood pressure was measured by the tail cuff technique and Th and catecholamines by HPLC with electrochemical detection.
In the animals receiving Sry there were significant increases after 3 weeks in resting plasma NE (57%) and adrenal Th content (49%) compared to vector controls. BP was 30 mmHg higher in Sry injected animals (160 mmHg, p < .05) compared to vector controls (130 mmHg) after 2-3 weeks. Histological analysis showed that the electroporation procedure did not produce morphological damage.
These results provide continued support that Sry is a candidate gene for hypertension. Also, these results are consistent with a role for Sry in increasing BP by directly or indirectly activating sympathetic nervous system activity.
我们实验室已经表明,SHR大鼠Y染色体上的一个基因座会升高SHR大鼠以及其基因组中导入了SHR Y染色体基因座的WKY大鼠(SHR/y大鼠)的血压。这个Y染色体高血压基因座的一个潜在候选基因是Sry,该基因编码一种负责睾丸发育的转录因子,并且Sry蛋白可能会影响其他靶基因。
以下研究检测了外源性Sry是否会升高肾上腺酪氨酸羟化酶(Th)、肾上腺儿茶酚胺、血浆儿茶酚胺和血压。我们通过电穿孔将10微克的表达构建体Sry1/pcDNA 3.1或对照载体导入WKY大鼠的肾上腺髓质。通过尾袖法测量血压,通过高效液相色谱电化学检测法测量Th和儿茶酚胺。
与载体对照组相比,接受Sry的动物在3周后静息血浆去甲肾上腺素(NE)显著增加(57%),肾上腺Th含量显著增加(49%)。2至3周后,注射Sry的动物的血压(160 mmHg,p <.05)比载体对照组(130 mmHg)高30 mmHg。组织学分析表明,电穿孔程序未产生形态学损伤。
这些结果进一步支持Sry是高血压的候选基因。此外,这些结果与Sry通过直接或间接激活交感神经系统活动来升高血压的作用一致。