Vascular contractile reactivity in hypotension due to reduced renal reabsorption of Na+ and restricted dietary Na+
Vascular contractile reactivity in hypotension due to reduced renal reabsorption of Na+ and restricted dietary Na+
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DOI：
10.1007/s00210-017-1340-0
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发表时间：
2017-03-01
影响因子：
3.6
通讯作者：
Soleimani, Manoocher
中科院分区：
文献类型：
--
作者：
Alshahrani, Saeed;Rapoport, Robert M.;Soleimani, Manoocher
肾脏Na+重吸收减少沿着限制饮食Na+消耗血管内血浆容量，从而导致低血压。是否发生低血压和低血压的程度部分取决于代偿性血管紧张素II介导的血管阻力增加。我们研究了血管阻力减轻低血压的能力是否受到收缩反应性降低的影响。在来自肾Na+重吸收减少和限制饮食Na+与相当大的低血压和肾素-血管紧张素系统激活相关的小鼠模型的主动脉中研究了体外反应性：（1）Na+-Cl-共转运蛋白（NCC）敲除（KO）与Na+限制饮食（0.1%，2周）和（2）相对更严重的pendrin（顶端氯/碳酸氢盐交换器）和NCC双KO。在两种模型的主动脉中，对KCl、苯丙氨酸和/或U46619的收缩敏感性保持不变。最大KCl和phenylalcohol收缩表示为力/主动脉长度从NCC KO与Na+限制饮食保持不变，而在pendrin/NCC双KO分别减少到49和64%。来自NCC KO和Na+限制饮食的主动脉湿重保持不变，而pendrin/NCC双KO降低至67%，与Verhoeff-Van Gieson染色测定的中膜宽度降低一致。这些结果表明，低血压与严重的血管内容量不足，作为减少肾Na+重吸收的结果，可能部分是由于减少血管肥大的结果减少收缩反应性。
Reduced renal Na+ reabsorption along with restricted dietary Na+ depletes intravascular plasma volume which can then result in hypotension. Whether hypotension occurs and the magnitude of hypotension depends in part on compensatory angiotensin II-mediated increased vascular resistance. We investigated whether the ability of vascular resistance to mitigate the hypotension was compromised by decreased contractile reactivity. In vitro reactivity was investigated in aorta from mouse models of reduced renal Na+ reabsorption and restricted dietary Na+ associated with considerable hypotension and renin-angiotensin system activation: (1) the Na+-Cl--Co-transporter (NCC) knockout (KO) with Na+ restricted diet (0.1%, 2 weeks) and (2) the relatively more severe pendrin (apical chloride/bicarbonate exchanger) and NCC double KO. Contractile sensitivity to KCl, phenylephrine, and/or U46619 remained unaltered in aorta from both models. Maximal KCl and phenylephrine contraction expressed as force/aorta length from NCC KO with Na+-restricted diet remained unaltered, while in pendrin/NCC double KO were reduced to 49 and 64%, respectively. Wet weight of aorta from NCC KO with Na+-restricted diet remained unaltered, while pendrin/NCC double KO was reduced to 67%, consistent with decreased medial width determined with Verhoeff-Van Gieson stain. These findings suggest that hypotension associated with severe intravascular volume depletion, as the result of decreased renal Na+ reabsorption, may in part be due to decreased contractile reactivity as a consequence of reduced vascular hypertrophy.