Cardiorenal Physiology and Medicine Section, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas.
Am J Physiol Renal Physiol. 2022 Sep 1;323(3):F349-F360. doi: 10.1152/ajprenal.00055.2022. Epub 2022 Jul 28.
Aromatase is a monooxygenase that catalyzes the rate-limiting step of estrogen biosynthesis from androgens. Aromatase inhibitors are widely used for the treatment of patients with hormone receptor-positive breast cancer. However, the effects of aromatase inhibitors on cardiovascular and renal health in females are understudied. Given that estrogen is protective against cardiovascular and kidney diseases, we hypothesized that aromatase inhibition elevates blood pressure and induces kidney injury in female Sprague-Dawley rats. Twelve-week-old female rats were implanted with radiotelemetry transmitters to continuously monitor blood pressure. After baseline blood pressure recording, rats were randomly assigned to treatment with the aromatase inhibitor anastrozole (ASZ) or vehicle (Veh) in drinking water. Twenty days after treatment initiation, rats were shifted from a normal-salt (NS) diet to a high-salt (HS) diet for an additional 40 days. Rats were euthanized 60 days after treatment initiation. Body weight increased in both groups over the study period, but the increase was greater in the ASZ-treated group than in the Veh-treated group. Mean arterial pressure increased in ASZ-treated rats during the NS and HS diet phases but remained unchanged in Veh-treated rats. In addition, urinary excretion of albumin and kidney injury marker-1 and plasma urea were increased in response to aromatase inhibition. Furthermore, histological assessment revealed that ASZ treatment increased morphological evidence of renal tubular injury and proximal tubular brush border loss. In conclusion, chronic aromatase inhibition in vivo with ASZ increases blood pressure and markers of renal proximal tubular injury in female Sprague-Dawley rats, suggesting an important role for aromatization in the maintenance cardiovascular and renal health in females. Aromatase enzyme catalyzes the rate-limiting step in estrogen biosynthesis. Aromatase inhibitors are clinically used for the treatment of patients with breast cancer; however, the impact of inhibiting aromatization on blood pressure and renal function is incompletely understood. The present findings demonstrate that systemic anastrozole treatment increases blood pressure and renal tubular injury markers in female rats fed a high-salt diet, suggesting an important role for aromatization in preserving cardiovascular and renal health in females.
芳香酶是一种单加氧酶，可催化从雄激素生物合成雌激素的限速步骤。芳香酶抑制剂广泛用于治疗激素受体阳性乳腺癌患者。然而，芳香酶抑制剂对女性心血管和肾脏健康的影响研究不足。鉴于雌激素对心血管和肾脏疾病具有保护作用，我们假设芳香酶抑制会升高女性 Sprague-Dawley 大鼠的血压并诱导肾脏损伤。将 12 周龄的雌性大鼠植入无线电遥测发射器以连续监测血压。在记录基础血压后，将大鼠随机分配到用芳香酶抑制剂阿那曲唑（ASZ）或载体（Veh）处理的饮用水中。在治疗开始后 20 天，大鼠从正常盐（NS）饮食转换为高盐（HS）饮食，再持续 40 天。在治疗开始后 60 天处死大鼠。在研究期间，两组大鼠的体重均增加，但 ASZ 治疗组的体重增加大于 Veh 治疗组。在 NS 和 HS 饮食阶段，ASZ 治疗大鼠的平均动脉压升高，但 Veh 治疗大鼠的平均动脉压不变。此外，芳香酶抑制会增加白蛋白和肾损伤标志物-1 的尿排泄以及血浆尿素。此外，组织学评估显示 ASZ 治疗增加了肾管状损伤和近端肾小管刷状缘丢失的形态学证据。总之，体内用 ASZ 进行慢性芳香酶抑制会增加雌性 Sprague-Dawley 大鼠的血压和肾近端小管损伤标志物，表明芳香化作用在维持女性心血管和肾脏健康方面的重要作用。芳香酶催化雌激素生物合成的限速步骤。芳香酶抑制剂在临床上用于治疗乳腺癌患者；然而，抑制芳香化作用对血压和肾功能的影响尚不完全清楚。本研究结果表明，全身给予阿那曲唑治疗会增加雌性大鼠高盐饮食中的血压和肾小管损伤标志物，表明芳香化作用在维持女性心血管和肾脏健康方面的重要作用。
