Department of Molecular Genetics, Biochemistry, and Microbiology, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
Am J Physiol Heart Circ Physiol. 2011 Oct;301(4):H1396-404. doi: 10.1152/ajpheart.00121.2011. Epub 2011 Aug 19.
The α(2)-isoform of Na,K-ATPase (α(2)) is thought to play a role in blood pressure regulation, but the specific cell type(s) involved have not been identified. Therefore, it is important to study the role of the α(2) in individual cell types in the cardiovascular system. The present study demonstrates the role of vascular smooth muscle α(2) in the regulation of cardiovascular hemodynamics. To accomplish this, we developed a mouse model utilizing the Cre/LoxP system to generate a cell type-specific knockout of the α(2) in vascular smooth muscle cells using the SM22α Cre. We achieved a 90% reduction in the α(2)-expression in heart and vascular smooth muscle in the knockout mice. Interestingly, tail-cuff blood pressure analysis reveals that basal systolic blood pressure is unaffected by the knockout of α(2) in the knockout mice. However, knockout mice do fail to develop ACTH-induced hypertension, as seen in wild-type mice, following 5 days of treatment with ACTH (Cortrosyn; wild type = 119.0 ± 6.8 mmHg; knockout = 103.0 ± 2.0 mmHg). These results demonstrate that α(2)-expression in heart and vascular smooth muscle is not essential for regulation of basal systolic blood pressure, but α(2) is critical for blood pressure regulation under chronic stress such as ACTH-induced hypertension.
α(2)-型钠钾 ATP 酶（α(2)）被认为在血压调节中发挥作用，但涉及的特定细胞类型尚未确定。因此，研究心血管系统中单个细胞类型的α(2)的作用非常重要。本研究证明了血管平滑肌α(2)在心血管血液动力学调节中的作用。为了实现这一目标，我们利用 Cre/LoxP 系统开发了一种小鼠模型，利用 SM22α Cre 在血管平滑肌细胞中特异性敲除α(2)。我们在敲除小鼠的心脏和血管平滑肌中实现了α(2)表达的 90%减少。有趣的是，尾套血压分析显示，α(2)在敲除小鼠中的敲除对基础收缩压没有影响。然而，与野生型小鼠相比，在接受 5 天 ACTH（Cortrosyn；野生型=119.0±6.8mmHg；敲除型=103.0±2.0mmHg）治疗后，敲除小鼠未能发展出 ACTH 诱导的高血压。这些结果表明，α(2)在心脏和血管平滑肌中的表达对于基础收缩压的调节不是必需的，但在慢性应激（如 ACTH 诱导的高血压）下，α(2)对血压调节至关重要。
