Effects of acute and subchronic AT1 receptor blockade on cardiovascular, hydromineral and neuroendocrine responses in female rats
Effects of acute and subchronic AT1 receptor blockade on cardiovascular, hydromineral and neuroendocrine responses in female rats
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DOI：
10.1016/j.physbeh.2013.08.018
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发表时间：
2013-10-02
影响因子：
2.9
通讯作者：
Mecawi, Andre Souza
中科院分区：
文献类型：
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作者：
Araujo, Iracema Gomes;Kagohara Elias, Lucila Leico;Mecawi, Andre Souza
切除雌性Wistar大鼠卵巢（OVX），并分成两组，连续14天接受环戊丙酸雌二醇（EC，40 μ g/kg，sc; OVX-EC）或载体（玉米油，Sc; OVX-油）。在处理的第7天，来自OVX-油和OVX-EC组的动物亚组经受亚慢性氯沙坦（AT（1）受体拮抗剂）处理（0.1g/L在饮用水中;类似于15 mg/kg/天）7天。另一组OVX油和OVX EC大鼠在激素替代的第14天接受急性氯沙坦注射（100 mg/kg，ip）。在两种方案中，测量以下参数：I）平均动脉压（MAP）和心率（HR）; II）水和0.3M盐水摄入量; III）血管紧张素II（ANG II）、心房利钠肽（ANP）、血管加压素（AVP）和催产素（OT）血浆浓度;以及IV）尿和血浆钠浓度。急性AT（1）阻断可导致OVX大鼠MAP显著降低，导致HR和饮水量增加，而雌二醇治疗可减弱这一作用。急性AT（1）阻断也增加ANG II和OT，降低血浆ANP浓度，而AVP分泌无变化。此外，急性低血压伴有尿钠排泄减少，雌二醇未改变尿钠排泄。亚慢性AT（1）阻断导致两组MAP显著降低，而HR无变化。此外，亚慢性氯沙坦治疗诱导OVX大鼠的钠食欲。延长AT，阻断增加ANG II和AVP，降低ANP血浆浓度。此外，它增加尿钠排泄，但不改变血浆OT浓度。最后，雌二醇治疗减弱了由亚慢性AT（1）阻滞引起的盐摄入量和血浆ANG II浓度的增加。总之，我们的研究结果表明，OVX和OVX-EC大鼠急性或亚慢性氯沙坦治疗的差异适应性反应。(C)2013 Elsevier Inc. All rights reserved.
Female Wistar rats were ovariectomized (OVX) and separated into two groups that received either estradiol cypionate (EC, 40 mu g/kg, sc; OVX-EC) or vehicle (corn oil, Sc; OVX-oil) for 14 consecutive days. On the 7th day of treatment, a subset of animals from both the OVX-oil and OVX-EC groups was subjected to subchronic losartan (AT(1) receptor antagonist) treatment (0.1 g/L in drinking water; similar to 15 mg/kg/day) for 7 days. Other group of OVX-oil and OVX-EC rats was submitted to an acute losartan injection (100 mg/kg, ip) on the 14th day of hormone replacement. In both protocols, the following parameters were measured: I) mean arterial pressure (MAP) and heart rate (HR); II) water and 0.3 M saline intake; III) angiotensin II (ANG II), atrial natriuretic peptide (ANP), vasopressin (AVP) and oxytocin (OT) plasma concentrations; and IV) urinary and plasma sodium concentrations. Acute AT(1) blockade induced a significant reduction in the MAP in the OVX rats, resulting in increased HR and water intake, which were attenuated by estradiol therapy. Acute AT(1) blockade also increased ANG II and OT and reduced ANP plasma concentrations, with no changes in AVP secretion. In addition, acute hypotension was accompanied by a decrease in natriuresis, which was unaltered by estradiol. Subchronic AT(1) blockade induced a significant decrease in MAP without changing HR in both groups. Additionally, subchronic losartan treatment induced sodium appetite in OVX rats. Prolonged AT, blockade increased ANG II and AVP and reduced ANP plasma concentrations. Moreover, it increased natriuresis but did not alter plasma OT concentrations. Finally, estradiol treatment attenuated the increase in salt intake and plasma ANG II concentrations induced by subchronic AT(1) blodcade. In conclusion, our results suggest differential adaptive responses to the acute or subchronic losartan treatment in OVX and OVX-EC rats. (C) 2013 Elsevier Inc. All rights reserved.