title: Knockout of the Na,K-ATPase α₂-isoform in the cardiovascular system does not alter basal blood pressure but prevents ACTH-induced hypertension.
abstract: 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.
authors.affiliation: Department of Molecular Genetics, Biochemistry, and Microbiology, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Tara N
authors.initials: TN
authors.lastname: Rindler
authors.forename: Iva
authors.initials: I
authors.lastname: Dostanic
authors.forename: Valerie M
authors.initials: VM
authors.lastname: Lasko
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Nieman
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Neumann
authors.forename: John N
authors.initials: JN
authors.lastname: Lorenz
authors.forename: Jerry B
authors.initials: JB
authors.lastname: Lingrel
mesh_terms: D000324:Adrenocorticotropic Hormone; D000818:Animals; D001794:Blood Pressure / Q000235:genetics* / Q000502:physiology*; D015153:Blotting, Western; D006332:Cardiomegaly / Q000378:metabolism; D002320:Cardiovascular Physiological Phenomena / Q000235:genetics; D002319:Cardiovascular System / Q000201:enzymology*; D002469:Cell Separation; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics* / Q000517:prevention & control*; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D016254:Mutagenesis, Insertional; D032383:Myocytes, Cardiac / Q000201:enzymology / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology / Q000502:physiology; D011995:Recombination, Genetic; D012039:Regional Blood Flow / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000502:physiology*; D014655:Vascular Resistance / Q000502:physiology
chemical_list: D008840:Microfilament Proteins; D009124:Muscle Proteins; C051615:transgelin; D000324:Adrenocorticotropic Hormone; C401838:Atp1a2 protein, mouse; D000254:Sodium-Potassium-Exchanging ATPase