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Knockout of the Na,K-ATPase α₂-isoform in the cardiovascular system does not alter basal blood pressure but prevents ACTH-induced hypertension.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2011 Oct; Vol. 301 (4), pp. H1396-404. Date of Electronic Publication: 2011 Aug 19. - Publication Year :
- 2011
-
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.
- Subjects :
- Animals
Blotting, Western
Cardiomegaly metabolism
Cardiovascular Physiological Phenomena genetics
Cell Separation
Hypertension chemically induced
Mice
Mice, Knockout
Microfilament Proteins metabolism
Microsomes metabolism
Muscle Proteins metabolism
Mutagenesis, Insertional
Myocytes, Cardiac enzymology
Myocytes, Cardiac physiology
Myocytes, Smooth Muscle enzymology
Myocytes, Smooth Muscle physiology
Recombination, Genetic
Regional Blood Flow physiology
Reverse Transcriptase Polymerase Chain Reaction
Sodium-Potassium-Exchanging ATPase genetics
Vascular Resistance physiology
Adrenocorticotropic Hormone
Blood Pressure genetics
Blood Pressure physiology
Cardiovascular System enzymology
Hypertension genetics
Hypertension prevention & control
Sodium-Potassium-Exchanging ATPase physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1539
- Volume :
- 301
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 21856916
- Full Text :
- https://doi.org/10.1152/ajpheart.00121.2011