Departamento de Bioquímica y Biología Molecular y Fisiología e Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid y CSIC, Valladolid, Spain.
J Physiol. 2012 Dec 1;590(23):6075-91. doi: 10.1113/jphysiol.2012.236190. Epub 2012 Sep 10.
The increased vascular tone that defines essential hypertension is associated with depolarization of vascular smooth muscle cells (VSMCs) and involves a change in the expression profile of ion channels promoting arterial contraction. As a major regulator of VSMC resting membrane potential (V(M)), K(+) channel activity is an important determinant of vascular tone and vessel diameter. However, hypertension-associated changes in the expression and/or modulation of K(+) channels are poorly defined, due to their large molecular diversity and their bed-specific pattern of expression. Moreover, the impact of these changes on the integrated vessel function and their contribution to the development of altered vascular tone under physiological conditions need to be confirmed. Hypertensive (BPH) and normotensive (BPN) mice strains obtained by phenotypic selection were used to explore whether changes in the functional expression of VSMC inward rectifier K(+) channels contribute to the more depolarized resting V(M) and the increased vascular reactivity of hypertensive arteries. We determined the expression levels of inward rectifier K(+) channel mRNA in several vascular beds from BPN and BPH animals, and their functional contribution to VSMC excitability and vascular tone in mesenteric arteries. We found a decrease in the expression of Kir2.1, Kir4.1, Kir6.x and SUR2 mRNA in BPH VSMCs, and a decreased functional contribution of both K(IR) and K(ATP) channels in isolated BPH VSMCs. However, only the effect of K(ATP) channel modulators was impaired when exploring vascular tone, suggesting that decreased functional expression of K(ATP) channels may be an important element in the remodelling of VSMCs in essential hypertension.
定义原发性高血压的血管张力增加与血管平滑肌细胞 (VSMC) 的去极化有关，涉及促进动脉收缩的离子通道表达谱的变化。作为 VSMC 静息膜电位 (V(M)) 的主要调节剂，K(+)通道活性是血管张力和血管直径的重要决定因素。然而，由于其分子多样性大且表达具有特定床型模式，与高血压相关的 K(+)通道表达和/或调节变化的定义较差。此外，这些变化对整合血管功能的影响及其对生理条件下改变的血管张力发展的贡献仍需要确认。通过表型选择获得的高血压 (BPH) 和正常血压 (BPN) 小鼠品系被用于探索 VSMC 内向整流 K(+)通道的功能表达变化是否有助于更去极化的静息 V(M) 和高血压动脉的血管反应性增加。我们确定了来自 BPN 和 BPH 动物的几种血管床中内向整流 K(+)通道 mRNA 的表达水平，以及它们对肠系膜动脉中 VSMC 兴奋性和血管张力的功能贡献。我们发现 BPH VSMC 中 Kir2.1、Kir4.1、Kir6.x 和 SUR2 mRNA 的表达减少，并且在分离的 BPH VSMC 中 K(IR)和 K(ATP)通道的功能贡献减少。然而，当探索血管张力时，只有 K(ATP)通道调节剂的作用受损，这表明 K(ATP)通道功能表达减少可能是原发性高血压中 VSMC 重塑的重要因素。
