Jones T J, Dunphy G, Milsted A, Ely D
Department of Biology, The University of Akron, Akron, Ohio, USA.
Hypertension. 1998 Nov;32(5):880-5. doi: 10.1161/01.hyp.32.5.880.
The Y chromosome in spontaneously hypertensive rats (SHR) and stroke-prone rats has been shown to contain a locus that contributes to the hypertensive effect; both the sympathetic nervous system and testosterone may be involved. The objective of this study was to look at the effects of testosterone on renal norepinephrine (NE) release and content in the isolated perfused kidney in different Y chromosome backgrounds. The study involved male SHR, Wistar-Kyoto rats (WKY), and 2 consomic strains with different Y chromosomes (n=5 to 8 per group). Adult animals were castrated, and implants containing testosterone propionate were placed at the base of the neck. Blood testosterone levels were measured by radioimmunoassay 2 weeks after castration. The left kidney was isolated and perfused with oxygenated Krebs solution at a constant flow and temperature with KCl and electrical stimulation of the renal nerves. Perfusate was collected and analyzed for NE by high-performance liquid chromatography. Lactate dehydrogenase analyses were performed as a marker for potential tissue damage. Renal perfusate and renal tissue NE levels were significantly elevated by testosterone. The average NE increase with a single testosterone implant was 13.2 ng/mL, and for a double testosterone implant it was 29.8 ng/mL. The Y chromosome from the SHR produced a significant increase in renal NE release compared with the WKY Y chromosome. Significance was shown between all groups: 1 versus 2 implants, P=0.0067; 1 versus sham implants, P=0.015; 2 versus sham implants, P<0.001. In conclusion, testosterone caused an enhanced renal NE release that was strain-specific, with the Y chromosome raising renal NE content and release.
自发性高血压大鼠(SHR)和易中风大鼠的Y染色体已被证明含有一个导致高血压效应的基因座;交感神经系统和睾酮可能都与之有关。本研究的目的是观察在不同Y染色体背景下,睾酮对离体灌注肾脏中去甲肾上腺素(NE)释放和含量的影响。该研究涉及雄性SHR、Wistar-Kyoto大鼠(WKY)以及2种具有不同Y染色体的染色体代换系(每组n = 5至8只)。成年动物接受阉割,并在颈部基部植入含有丙酸睾酮的植入物。阉割后2周通过放射免疫测定法测量血液睾酮水平。分离出左肾,用含氧量的Krebs溶液在恒定流量和温度下灌注,并加入氯化钾以及对肾神经进行电刺激。收集灌注液,通过高效液相色谱法分析NE。进行乳酸脱氢酶分析作为潜在组织损伤的标志物。睾酮使肾灌注液和肾组织NE水平显著升高。单次植入睾酮时NE平均增加13.2 ng/mL,双次植入时为29.8 ng/mL。与WKY Y染色体相比,SHR的Y染色体使肾NE释放显著增加。所有组之间均显示出显著性差异:1次植入与2次植入相比,P = 0.0067;1次植入与假植入相比,P = 0.015;2次植入与假植入相比,P < 0.001。总之,睾酮导致肾NE释放增强,且具有品系特异性,Y染色体可提高肾NE含量和释放。