Acutely, testosterone (TES) and other androgens are efficacious vasodilators, both in vitro and in vivo; however, their long-term effects on arterial blood pressure (BP) remain unclear. It was hypothesized that endogenous androgens exert long-term anti-hypertensive effects on systemic BP through a combination of genomic and nongenomic effects to enhance vasodilation of the systemic vasculature. The long-term effects of endogenous TES and exogenous TES replacement therapy (TRT) on BP were studied in intact (InT) and castrated (CsX) male Sprague-Dawley (SD) and testicular-feminized male (Tfm, androgen receptor defective) rats (12 weeks old). Systolic BP (tail-cuff plethysmography) was determined weekly for 15 weeks in InT-control and CsX rats. Some CsX-SD rats received androgen replacement therapy at 10-15 weeks with TES-enanthate (TRT; 1.75 mg/kg, 2x/week) or DHT-enanthate (DRT; 1.00 mg/kg. 2x/week) and a separate group of CsX-SD rats received losartan-potassium in drinking water (LST, 250 mg/L) for the entire 15 week period. Expression of renin, angiotensinogen (Agt), angiotensin converting enzyme (ACE), and angiotensin II type I receptor (AT1R) mRNA in kidney and aorta were determined by real-time PCR (rt-PCR) and plasma renin levels were determined by radioimmunoassay. There was a progressive rise in BP over 10 weeks in CsX (109 ± 3.3 vs. 143 ± 3.5 mmHg), while BP remained stable in InT-control (109 ± 3.0 vs. 113 ± 0.3). BP gradually declined to normal in CsX-TRT rats (113 ± 1.3), while BP remained elevated in CsX (140 ± 1.2) and normal in InT-control (113 ± 0.3). LST prevented the development of hypertension in CsX at 10 weeks (100 ± 1.5 in CsX + LST vs. 143 ± 3.5 in CsX). During the next 5 weeks with TES-RT, BP declined in CsX-TRT (113 ± 1.3) and remained lower in CsX + LST (99 ± 0.4). DHT-RT reduced BP in CxS to a similar extent. In Tfm, CsX resulted in a similar rise in BP (109 ± 0.7 vs. 139 ± 0.4 mmHg), but TRT reduced BP more rapidly and to a greater extent (106 ± 2.8). rt-PCR of the kidney revealed that CsX increased expression of mRNA for renin (92%), ACE (58%), and AT1R (80%) compared to InT, while TES RT normalized expression of renin, AT1R, and ACE mRNA to levels of InT rats. Plasma renin levels exhibited changes similar to those observed for renin mRNA expression. This is the first study to examine the long-term effects of endogenous and exogenous androgens on BP in male SD and Tfm rats. These data reveal that endogenous androgens (TES) exert anti-hypertensive effects that appear to involve non-genomic and possibly genomic mechanism(s), resulting in reductions in RAS expression in the kidney and enhanced systemic vasodilation.

中文翻译：

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雄性 Sprague-Dawley 大鼠的性腺高血压是肾素-血管紧张素系统依赖性的：内源性雄激素的作用。

急性地，睾酮 (TES) 和其他雄激素是有效的体外和体内血管扩张剂；然而，它们对动脉血压 (BP) 的长期影响仍不清楚。假设内源性雄激素通过基因组和非基因组作用的组合对全身性血压产生长期抗高血压作用，以增强全身血管系统的血管舒张。在完整 (InT) 和去势 (CsX) 雄性 Sprague-Dawley (SD) 和睾丸女性化雄性（Tfm，雄激素受体缺陷）大鼠中研究了内源性 TES 和外源性 TES 替代疗法 (TRT) 对 BP 的长期影响（12 周大）。在 InT 对照和 CsX 大鼠中每周测定收缩压（尾袖体积描记法），持续 15 周。一些 CsX-SD 大鼠在 10-15 周时接受了 TES-庚酸盐（TRT；1.75 mg/kg，2 次/周）或 DHT-庚酸盐（DRT；1.00 毫克/公斤。2 次/周）和一组单独的 CsX-SD 大鼠在整个 15 周期间接受饮用水中的氯沙坦钾（LST，250 毫克/升） . 肾素、血管紧张素原 (Agt)、血管紧张素转化酶 (ACE) 和血管紧张素 II I 型受体 (AT1R) mRNA 在肾脏和主动脉中的表达通过实时 PCR (rt-PCR) 测定，血浆肾素水平通过放射免疫测定法测定. CsX 的血压在 10 周内逐渐升高（109 ± 3.3 对 143 ± 3.5 mmHg），而 InT 控制组的血压保持稳定（109 ± 3.0 对 113 ± 0.3）。CsX-TRT 大鼠的血压逐渐下降至正常 (113 ± 1.3)，而 CsX (140 ± 1.2) 的血压仍然升高，InT 控制组的血压正常 (113 ± 0.3)。LST 在 10 周时阻止了 CsX 高血压的发展（CsX + LST 为 100 ± 1.5，而 CsX 为 143 ± 3.5）。在接下来的 5 周内，使用 TES-RT，CsX-TRT 的血压下降 (113 ± 1.3)，而 CsX + LST 的血压保持较低 (99 ± 0.4)。DHT-RT 将 CxS 中的血压降低到类似的程度。在 Tfm 中，CsX 导致类似的血压升高（109 ± 0.7 与 139 ± 0.4 mmHg），但 TRT 降低血压的速度更快，幅度更大（106 ± 2.8）。肾脏的 rt-PCR 显示，与 InT 相比，CsX 增加了肾素 (92%)、ACE (58%) 和 AT1R (80%) 的 mRNA 表达，而 TES RT 使肾素、AT1R 和 ACE mRNA 的表达正常化至InT 大鼠的水平。血浆肾素水平表现出类似于肾素 mRNA 表达所观察到的变化。这是第一项研究内源性和外源性雄激素对雄性 SD 和 Tfm 大鼠血压的长期影响。