Estrogen Metabolite 2-Methoxyestradiol Attenuates Blood Pressure in Hypertensive Rats by Downregulating Angiotensin Type 1 Receptor.
Estrogen Metabolite 2-Methoxyestradiol Attenuates Blood Pressure in Hypertensive Rats by Downregulating Angiotensin Type 1 Receptor.
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DOI：
10.3389/fphys.2022.876777
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发表时间：
2022
影响因子：
4
通讯作者：
中科院分区：
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2-甲氧乙烯醚（2 ME 2）在心血管疾病中的治疗潜力是显而易见的。我们的实验室先前已经证明了2 ME 2在体外调节血管紧张素1型受体（AT 1 R）的机制。然而，2 ME 2对血管紧张素受体的调节及其对血压（BP）和静息心率（RHR）的影响尚不确定。在这项研究中，输注血管紧张素II（65 ng/min）的雄性和雌性Wistar-Kyoto（WKY）大鼠和雄性自发性高血压大鼠（SHR）通过手术植入遥测探针，以连续评估动脉BP和RHR。在雄性和雌性WKY大鼠中，2 ME 2治疗（20 mg/kg/天，持续2周）导致Ang II诱导的收缩压、舒张压和平均动脉血压显著降低。此外，在所有组中均显示了显著的体重减轻和RHR。在一组单独的实验中，雄性SHR长期暴露于2 ME 2（20 mg/kg/天，持续5周）显示舒张压和平均动脉血压沿着RHR显著降低。我们还发现肾脏和肝脏中血管紧张素受体和血管紧张素原（AGT）的下调以及血浆Ang II水平的降低。总的来说，我们证明，2 ME 2衰减血压和RHR在高血压大鼠涉及血管紧张素受体和体重减轻下调。
The therapeutic potential of 2-Methoxyestradiol (2ME2) is evident in cardiovascular disease. Our laboratory has previously demonstrated the mechanism involved in the 2ME2 regulation of angiotensin type 1 receptor (AT1R) in vitro. However, 2ME2 regulation of angiotensin receptors and its effects on blood pressure (BP) and resting heart rate (RHR) are uncertain. In this study, male and female Wistar-Kyoto (WKY) rats infused with angiotensin II (65 ng/min) and male spontaneously hypertensive rats (SHR) were surgically implanted with telemetric probes to continuously assess arterial BP and RHR. In both male and female WKY rats, 2ME2 treatment (20 mg/kg/day for 2 weeks) resulted in a significant reduction of Ang II-induced systolic, diastolic, and mean arterial BP. Moreover, significant weight loss and RHR were indicated in all groups. In a separate set of experiments, prolonged 2ME2 exposure in male SHR (20 mg/kg/day for 5 weeks) displayed a significant reduction in diastolic and mean arterial BP along with RHR. We also found downregulation of angiotensin receptors and angiotensinogen (AGT) in the kidney and liver and a reduction of plasma Ang II levels. Collectively, we demonstrate that 2ME2 attenuated BP and RHR in hypertensive rats involves downregulation of angiotensin receptors and body weight loss.
影响因子：
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作者：
Koganti S;Snyder R;Thekkumkara T
通讯作者：
Thekkumkara T