From the Director's Research Group (A.K.S., G.L.J.), Department of Vascular Pharmacology (A.K.S., K.L.A., J.P.F.C.-D.), Department of Neuropharmacology (G.A.H.), and Department of Diabetic Complications (M.C.T.), Baker IDI Heart and Diabetes Institute, Melbourne, Australia; and Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (D.G., M.W.M., A.F.D.).
Hypertension. 2014 Dec;64(6):1376-83. doi: 10.1161/HYPERTENSIONAHA.114.03756. Epub 2014 Sep 8.
The lineage of the Y chromosome accounts for up to 15 to 20 mm Hg in arterial pressure. Genes located on the Y chromosome from the spontaneously hypertensive rat (SHR) are associated with the renin-angiotensin system. Given the important role of the renin-angiotensin system in the renal regulation of fluid homeostasis and arterial pressure, we hypothesized that the origin of the Y chromosome influences arterial pressure via interaction between the intrarenal vasculature and the renin-angiotensin system. Sixteen-week-old normotensive rats (Wistar Kyoto [WKY]), spontaneously hypertensive stroke-prone rat (SHRSP), and 2 reciprocal Y consomic rat strains, 1 comprising the WKY autosomes and X chromosome with the Y chromosome from the hypertensive rat strain (WKY.SPGlaY) and vice versa (SP.WKYGlaY), were examined. SP.WKYGlaY had lower systolic blood pressure than SHRSP (195±5 versus 227±8 mm Hg; P<0.03), whereas WKY.SPGlaY had higher systolic blood pressure compared with WKY (157±3 versus 148±3 mm Hg; P<0.05), measured by radiotelemetry. Compared with WKY rats, SHRSP had higher plasma angiotensin(1-7) (Ang (1-7)):Ang II ratio (WKY: 0.13±0.01 versus SHRSP: 1.33±0.4; P<0.005), greater angiotensin II receptor type 2 and Mas receptor mRNA expression, and a blunted renal constrictor response to intrarenal Ang I and Ang(1-7) infusions. Introgression of the normotensive Y chromosome into the SHRSP background (SP.WKYGlaY) restored responses in the SHRSP to WKY levels, evidenced by a reduction in plasma Ang(1-7):Ang II ratio (SP.WKYGlaY: 0.24±0.02; P<0.01), angiotensin II receptor type 2, and Mas receptor mRNA expression and an increased vasoconstrictor response to intrarenal Ang I and Ang(1-7) infusion. This study demonstrates that the origin of the Y chromosome significantly impacts the renal vascular responsiveness and therefore may influence the long-term renal regulation of blood pressure.
Y 染色体的谱系解释了动脉血压中高达 15 到 20 毫米汞柱的变化。自发性高血压大鼠 (SHR) 上位于 Y 染色体上的基因与肾素-血管紧张素系统有关。鉴于肾素-血管紧张素系统在肾脏调节液体平衡和动脉血压方面的重要作用，我们假设 Y 染色体的起源通过肾内血管系统与肾素-血管紧张素系统的相互作用影响动脉血压。我们检查了 16 周龄的正常血压大鼠 (Wistar Kyoto [WKY])、自发性高血压卒中倾向大鼠 (SHRSP) 和 2 个相互的 Y 染色体同源性大鼠品系，1 个包含 WKY 常染色体和 X 染色体，而 Y 染色体来自高血压大鼠品系 (WKY.SPGlaY)，反之亦然 (SP.WKYGlaY)。SP.WKYGlaY 的收缩压低于 SHRSP(195±5 对 227±8 毫米汞柱；P<0.03)，而 WKY.SPGlaY 的收缩压高于 WKY(157±3 对 148±3 毫米汞柱；P<0.05)，通过无线电遥测测量。与 WKY 大鼠相比，SHRSP 具有更高的血浆血管紧张素(1-7) (Ang (1-7))：Ang II 比值 (WKY：0.13±0.01 对 SHRSP：1.33±0.4；P<0.005)，更高的血管紧张素 II 受体 2 型和 Mas 受体 mRNA 表达，以及肾内 Ang I 和 Ang(1-7)输注的肾血管收缩反应减弱。将正常血压的 Y 染色体导入 SHRSP 背景 (SP.WKYGlaY)，通过降低血浆 Ang(1-7)：Ang II 比值 (SP.WKYGlaY：0.24±0.02；P<0.01)、血管紧张素 II 受体 2 型和 Mas 受体 mRNA 表达以及增加肾内 Ang I 和 Ang(1-7)输注的血管收缩反应，使 SHRSP 的反应恢复到 WKY 水平。这项研究表明，Y 染色体的起源显著影响肾脏血管的反应性，因此可能影响血压的长期肾脏调节。
