Knockout of the Na,K-ATPase α2-isoform in the cardiovascular system does not alter basal blood pressure but prevents ACTH-induced hypertension

The α2-isoform of Na,K-ATPase (α2) 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 α2 in individual cell types in the cardiovascular system. The present study demonstrates the role of vascular smooth muscle α2 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 α2 in vascular smooth muscle cells using the SM22α Cre. We achieved a 90% reduction in the α2-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 α2 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 α2-expression in heart and vascular smooth muscle is not essential for regulation of basal systolic blood pressure, but α2 is critical for blood pressure regulation under chronic stress such as ACTH-induced hypertension.