Evidence for endothelin involvement in the response to high salt

Evidence for endothelin involvement in the response to high salt
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DOI:
10.1152/ajprenal.2001.281.1.f144
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发表时间:
2001-07-01
影响因子:
4.2
通讯作者:
Pollock, JS
Pollock, JS
中科院分区:
医学2区
文献类型:
--
作者:
Pollock, DM;Pollock, JS

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最近的证据表明,内皮素-1 (ET-1) 可能通过 ET(B) 受体,通过控制钠排泄参与血压调节。通过遥测植入物连续测量雄性 Sprague-Dawley 大鼠的平均动脉压 (MAP)。 1周后。在基线测量中,在实验的剩余时间里,给大鼠喂食高(10%)或低(0.08%)氯化钠食物(每组 n = 5)。与低盐饮食大鼠 (103 +/- 2 mmHg;P < 0.05) 相比,高盐饮食大鼠 (115 +/- 2 mmHg) MAP 显着增加。然后用与食物混合的ET(B)受体拮抗剂A-192621治疗所有大鼠,并每日调整以确保剂量为30 mg.kg(-1).day(-1)。 ET(B) 阻断在治疗的几个小时内导致 MAP 增加,并且在 1 周内高盐饮食的大鼠中显着升高(170 +/- 3 与 115 +/- 3 mmHg,P < 0.01)。为了确定 A-192621 治疗期间 MAP 的增加是否是由于 ET(A) 受体激活增加所致,所有大鼠在饮用水中给予 ET(A) 选择性拮抗剂 ABT-627,同时继续低盐/高盐饮食和 ET(B) 阻断。 ABT-627 在高盐 (113 +/- 3 mmHg) 或低盐 (101 +/- 3 mmHg) 饮食的大鼠中数小时内降低了 MAP。这些结果支持这样的假设:内皮素通过 ET(B) 受体参与盐负荷反应中的血压调节。
Recent evidence suggests that endothelin-1 (ET-1), perhaps through the ET(B) receptor, may participate;in blood pressure regulation through the control of sodium excretion. Mean arterial pressure (MAP) was continuously measured via telemetry implants in male Sprague-Dawley rats. After 1 wk. of baseline measurements, rats were given either high (10%) or low (0.08%) NaCl in chow for the remainder of the experiment (n = 5 in each group). MAP was significantly increased in rats on a high-salt diet (115 +/- 2 mmHg) compared with rats on the low-salt diet (103 +/- 2 mmHg; P < 0.05). All rats were then treated with the ET(B) receptor antagonist A-192621 mixed with the food and adjusted daily to ensure a dose of 30 mg.kg(-1).day(-1). ET(B) blockade produced an increase in MAP within a few hours of treatment and was significantly higher in rats on the high-salt diet over a 1-wk period (170 +/- 3 vs. 115 +/- 3 mmHg, P < 0.01). To determine whether the increase in MAP during A-192621 treatment was due to increased ET(A) receptor activation, all rats were then given the ET(A)-selective antagonist ABT-627 in the drinking water while a low-salt/high-salt diet and ET(B) blockade were continued. ABT-627 decreased MAP within a few hours in rats on either the high-salt (113 +/- 3 mmHg) or low-salt (101 +/- 3 mmHg) diet. These results support the hypothesis that endothelin, through the ET(B) receptor, participates in blood pressure regulation in the response to salt loading.