Choopani Samira, Nematbakhsh Mehdi
Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran.
Int J Vasc Med. 2021 Mar 1;2021:6643485. doi: 10.1155/2021/6643485. eCollection 2021.
High blood pressure is one of the most important causes of death around the world. The renin-angiotensin system (RAS) and estradiol are two important items that regulate arterial blood pressure in women. However, hypertension, RAS, and sex hormone estradiol may influence renal vascular responses. This study was designed to determine the role of Mas receptor (MasR) on renal vascular response to angiotensin II (Ang II) administration in two kidneys-one clip (2K1C) hypertensive rats treated with estradiol.
The ovariectomized rats were subjected to 2K1C or non-2K1C and simultaneously treated with estradiol (500 g/kg/weekly) or placebo for a period of 4 weeks. Subsequently, under anesthesia, renal vascular responses to graded doses of Ang II administration with MasR blockade (A779) or its vehicle were determined.
A779 or its vehicle did not alter mean arterial pressure (MAP), renal perfusion pressure (RPP), and renal blood flow (RBF). However, in non-2K1C rats, Ang II infusion decreased RBF and increased renal vascular resistance (RVR) responses in a dose-related manner (treat < 0.0001). The greatest responses were found in ovariectomized estradiol-treated rats that received A779 (group < 0.05) in non-2K1C rats. Such findings were not detected in 2K1C hypertensive rats. For example, in estradiol-treated rats that received A779, at 1000 ng/kg/min of Ang II infusion, RBF reduced from 1.6 ± 0.2 to 0.89 ± 0.19 ml/min in non-2K1C rats, and it reduced from 1.6 ± 0.2 to 1.2 ± 0.2 ml/min in 2K1C rats.
Hypertension induced by 2K1C may attenuate the role of A779 and estradiol in renal vascular responses to Ang II infusion. Perhaps, this response can be explained by the reduction of Ang II type 1 receptor (AT1R) expression in the 2K1C hypertensive rats.
高血压是全球最重要的死亡原因之一。肾素 - 血管紧张素系统（RAS）和雌二醇是调节女性动脉血压的两个重要因素。然而，高血压、RAS和性激素雌二醇可能会影响肾血管反应。本研究旨在确定Mas受体（MasR）在接受雌二醇治疗的两肾一夹（2K1C）高血压大鼠中对血管紧张素II（Ang II）给药的肾血管反应中的作用。
将去卵巢大鼠分为2K1C组或非2K1C组，并同时用雌二醇（500μg/kg/周）或安慰剂治疗4周。随后，在麻醉状态下，测定给予MasR阻滞剂（A779）或其溶剂时，肾血管对不同剂量Ang II给药的反应。
A779或其溶剂未改变平均动脉压（MAP）、肾灌注压（RPP）和肾血流量（RBF）。然而，在非2K1C大鼠中，Ang II输注以剂量相关方式降低RBF并增加肾血管阻力（RVR）反应（处理<0.0001）。在接受A779的去卵巢雌二醇治疗大鼠中发现最大反应（组<0.05），在非2K1C大鼠中。在2K1C高血压大鼠中未检测到此类结果。例如，在接受A779的雌二醇治疗大鼠中，在输注1000ng/kg/min的Ang II时，非2K1C大鼠的RBF从1.6±0.2降至0.89±0.19ml/min，而2K1C大鼠的RBF从1.6±0.2降至1.2±0.2ml/min。
2K1C诱导的高血压可能减弱A779和雌二醇在肾血管对Ang II输注反应中的作用。也许，这种反应可以通过2K1C高血压大鼠中血管紧张素II 1型受体（AT1R）表达的降低来解释。
