Physiological Role of the α2-Isoform of the Na, K-ATPase in the Regulation of Cardiovascular Function
type: CreativeWork
description: Na,K-ATPase is a ubiquitously expressed heteromeric transmembrane protein composed of two essential subunits: α and β. There are four known isoforms of the catalytic α-subunit (α1, α2, α3, and α4), and each isoform displays a unique tissue distribution and expression pattern suggesting a tissue-specific role for the α-subunits. The α2-isoform of the Na,K-ATPase (α2) is the minor isoform of the Na,K-ATPase expressed in the cardiovascular system but is thought play a critical role in the regulation of systolic blood pressure (SBP). However, the organ system/cell type expressing α2 that is required for this regulation has not been fully defined. The present dissertation study uses tissue-specific knockouts of α2 to further define the tissue-specific role of the α2 in the regulation of SBP. To accomplish this, we developed a mouse model utilizing the Cre/LoxP system to generate tissue-specific knockouts of α2 in the vascular smooth muscle and heart using mice expressing Cre recombinase in a smooth muscle and cardiac-specific manner. Using the SM22α Cre we generated a smooth muscle-specific knockout (SMα2-/-) mouse with a 90% reduction in α2-expression in heart and vascular smooth muscle. Interestingly, tail-cuff blood pressure analysis reveals that SBP is unaffected by the smooth muscle-specific knockout of α2. However, the SMα2-/- mice do fail to develop ACTH-induced hypertension, as seen in control mice in response to ACTH treatment (Control=119±7, SMα2-/-=103±2 mmHg). In addition, utlizing the β-MHC Cre we generated a heart-specific knockout (βMHCα2-/-) mouse with a 90% reduction in α2-expression that is specific to the heart. βMHCα2-/- mice exhibit normal basal SBP, and in addition these mice develop ACTH-induced hypertension in response to ACTH treatment similar to control mice (Control=119±3, βMHCα2-/-=117±6 mmHg). Surprisingly, βMHCα2-/- mice display delayed onset of cardiac dysfunction compared to control mice in response to pressure-overload induced by transaor…
abstract: Na,K-ATPase is a ubiquitously expressed heteromeric transmembrane protein composed of two essential subunits: α and β. There are four known isoforms of the catalytic α-subunit (α1, α2, α3, and α4), and each isoform displays a unique tissue distribution and expression pattern suggesting a tissue-specific role for the α-subunits. The α2-isoform of the Na,K-ATPase (α2) is the minor isoform of the Na,K-ATPase expressed in the cardiovascular system but is thought play a critical role in the regulation of systolic blood pressure (SBP). However, the organ system/cell type expressing α2 that is required for this regulation has not been fully defined. The present dissertation study uses tissue-specific knockouts of α2 to further define the tissue-specific role of the α2 in the regulation of SBP. To accomplish this, we developed a mouse model utilizing the Cre/LoxP system to generate tissue-specific knockouts of α2 in the vascular smooth muscle and heart using mice expressing Cre recombinase in a smooth muscle and cardiac-specific manner. Using the SM22α Cre we generated a smooth muscle-specific knockout (SMα2-/-) mouse with a 90% reduction in α2-expression in heart and vascular smooth muscle. Interestingly, tail-cuff blood pressure analysis reveals that SBP is unaffected by the smooth muscle-specific knockout of α2. However, the SMα2-/- mice do fail to develop ACTH-induced hypertension, as seen in control mice in response to ACTH treatment (Control=119±7, SMα2-/-=103±2 mmHg). In addition, utlizing the β-MHC Cre we generated a heart-specific knockout (βMHCα2-/-) mouse with a 90% reduction in α2-expression that is specific to the heart. βMHCα2-/- mice exhibit normal basal SBP, and in addition these mice develop ACTH-induced hypertension in response to ACTH treatment similar to control mice (Control=119±3, βMHCα2-/-=117±6 mmHg). Surprisingly, βMHCα2-/- mice display delayed onset of cardiac dysfunction compared to control mice in response to pressure-overload induced by transaor…
author: Rindler, Tara N.
language: English
keywords: Biochemistry, Microbiology, Genetics, Adrenocorticotropic hormone, Endogenous cardiac glycosides, Hypertension, Ouabain, Systolic Blood Pressure, Transaortic constriction
date published: 2012
date modified: 2026-07-24T03:36:39Z
provider: OhioLINK
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cincinnati