Role of α-adrenergic receptor subtypes in the acute hypertensive response to hypertonic saline infusion in anephric mice
Role of α-adrenergic receptor subtypes in the acute hypertensive response to hypertonic saline infusion in anephric mice
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DOI：
10.1161/01.hyp.35.2.609
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发表时间：
2000-02-01
期刊：
影响因子：
8.3
通讯作者：
Gavras, H
中科院分区：
文献类型：
--
作者：
Makaritsis, KP;Johns, C;Gavras, H
实验证据表明，高渗盐水诱导的无肾动物急性高血压反应是通过抑制中枢神经系统突触前交感神经抑制性α(2)-肾上腺素能受体(α(2)-AR)介导的。本实验的目的是剖析三种不同的α(2)-AR亚型(α(2A)-、α(2B)-和α(2C)-AR)在这一反应中的作用。每组缺乏这些α(2)-AR亚型基因的基因工程小鼠接受双侧肾切除，然后在持续的直接血压(BP)监测下，在2小时内注入0.4毫升4%的生理盐水。阿尔法(2A)-AR缺陷和阿尔法(2C)-AR缺陷小鼠的血压显著升高(分别为11.8+/-2.5和16.7+/-1.7毫米汞柱)，野生型小鼠(分别为17.8+/-2.5和11.8+/-2.0毫米汞)和野生型阿尔法(2B)+/+(13.1+/-2.4毫米汞)也是如此。然而，阿尔法(2B)-AR缺陷小鼠不能升高他们的血压，并且在输液期结束时血压略有下降(下降了-3.0+/-4.0 mm Hg)。所有6组患者的血浆去甲肾上腺素水平均升高，在输液结束时介于0.8至1.8 ng/ml之间。在所有情况下，阿尔法(2)-AR缺陷组的去甲肾上腺素水平往往高于野生型对应组。令人惊讶的是，这种差异只在阿尔法(2B)-AR缺陷小鼠中显著，尽管去甲肾上腺素升高，但它们的血压却无法上升。这些数据表明，需要完整的α(2B)-AR来调节高血压对急性生理盐水负荷的反应，即使在这种情况下它的缺失并不能阻止去甲肾上腺素的释放。
Experimental evidence suggests that the acute hypertensive response induced in anephric animals by infusion of a hypertonic saline solution is mediated by disinhibition of the presynaptic sympathoinhibitory alpha(2)-adrenergic receptors (alpha(2)-AR) of the central nervous system. The purpose of the present experiments was to dissect the role of the 3 distinct alpha(2)-AR subtypes (alpha(2A)-, alpha(2B), - and alpha(2C)-AR) in this response. Groups of genetically engineered mice deficient in each one of these alpha(2)-AR subtype genes were submitted to bilateral nephrectomy followed by a 0.4-mL infusion of 4% saline over a 2-hour period, with constant direct blood pressure (BP) monitoring. The alpha(2A)-AR-deficient and (alpha(2C)-AR-deficient mice responded with significant BP elevations (by 11.8 +/- 2.5 and 16.7 +/- 1.7 mm Hg, respectively), and so did their wild-type counterparts (17.8+/-2.5 and 11.8+/-2.0 mmHg, respectively) and the wild-type alpha(2B) +/+ (13.1+/-2.4 mm Hg). However, the alpha(2B)-AR-deficient mice were unable to raise their BP and had a slightly lowered BP (by -3.0+/-4.0 mm Hg) at the end of the infusion period. All 6 groups exhibited elevated plasma norepinephrine levels ;ranging between 0.8 and 1.8 ng/mL at the end of the infusion. In all cases, the alpha(2)-AR-deficient groups tended to have higher norepinephrine levels than their wild-type counterparts. Surprisingly, this difference was significant only in the alpha(2B)-AR-deficient mice, which, despite the elevated norepinephrine, were unable to raise their BP. The data suggest that a full complement of the alpha(2B)-AR is needed to mediate the hypertensive response to acute saline load, even though its absence does not prevent the release of norepinephrine under these conditions.