There is a sex difference in hypertensive renal injury, with men experiencing greater severity and a more rapid progression of renal disease than women; however, the molecular mechanisms protecting against renal injury in women are unknown. The goal of this study was to determine whether sex hormones modulate blood pressure and the progression of albuminuria during the developmental phase of hypertension in male and female spontaneously hypertensive rats (SHR). Studies were also performed to examine how sex and sex hormones influence two major risk factors for albuminuria, overactivation of the renin-angiotensin system and oxidative stress. Blood pressure was measured by telemetry in gonad-intact and gonadectomized male and female SHR. Microalbumin excretion, measured over time, and macrophage infiltration were used to assess renal health. Male SHR had significantly higher blood pressures than female SHR, and gonadectomy decreased blood pressures in males with no effect in females. Male SHR displayed a gonad-sensitive increase in albuminuria over time, and female SHR had a gonad-sensitive suppression in macrophage infiltration. Female SHR had greater plasma ANG II levels and similar levels of renal cortical ANG II vs. levels shown in males but less AT(1)-receptor protein expression in the renal cortex. Female SHR also had a gonad-sensitive decrease in renal oxidative stress. Therefore, the renal protection afforded to female SHR is associated with lower blood pressure, decreased macrophage infiltration, and decreased levels of oxidative stress.

译文

高血压肾损伤存在性别差异,男性比女性更严重,肾脏疾病进展更快; 然而,保护女性肾损伤的分子机制尚不清楚。这项研究的目的是确定性激素是否在男性和女性自发性高血压大鼠 (SHR) 的高血压发育期调节血压和蛋白尿的进展。还进行了研究,以检查性别和性激素如何影响蛋白尿的两个主要危险因素,肾素-血管紧张素系统的过度激活和氧化应激。通过遥测测量性腺完整和性腺切除的男性和女性SHR的血压。随时间推移测量的微量白蛋白排泄和巨噬细胞浸润用于评估肾脏健康。男性SHR的血压明显高于女性SHR,性腺切除术可降低男性的血压,而女性则无影响。随着时间的推移,男性SHR表现出对性腺敏感的蛋白尿增加,而女性SHR在巨噬细胞浸润中表现出对性腺敏感的抑制。与男性相比,女性SHR的血浆ANG II水平更高,肾皮质ANG II水平相似,但肾皮质中AT(1)-受体蛋白表达较少。女性SHR在肾脏氧化应激中也具有性腺敏感性降低。因此,对女性SHR提供的肾脏保护与降低血压,减少巨噬细胞浸润和降低氧化应激水平有关。

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