Document Detail


Transgenic mice expressing Na+-K+-ATPase in smooth muscle decreases blood pressure.
MedLine Citation:
PMID:  17468335     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Na(+)-K(+)-ATPase (NKA) is a transmembrane protein that sets and maintains the electrochemical gradient by extruding three Na(+) in exchange for two K(+). An important physiological role proposed for vascular smooth muscle NKA is the regulation of blood pressure via modulation of vascular smooth muscle contractility (5). To investigate the relations between the level of NKA in smooth muscle and blood pressure, we developed mice carrying a transgene for either the NKA alpha(1)- or alpha(2)-isoform (alpha(1 sm+) or alpha(2 sm+) mice) driven by the smooth muscle-specific alpha-actin promoter SMP8. Interestingly, both alpha-isoforms, the one contained in the transgene and the one not contained, were increased to a similar degree at both protein and mRNA levels. The total alpha-isoform protein was increased from 1.5-fold (alpha(1 sm+) mice) to 7-fold (alpha(2 sm+) mice). The increase in total NKA alpha-isoform protein was accompanied by a 2.5-fold increase in NKA activity in alpha(2 sm+) gastric antrum. Immunocytochemistry of the alpha(1)- and alpha(2)-isoforms in alpha(2 sm+) aortic smooth muscle cells indicated that alpha-isoform distributions were similar to those shown in wild-type cells. alpha(2 sm+) Mice (high expression) were hypotensive (109.9 +/- 1.6 vs. 121.3 +/- 1.4 mmHg; n = 13 and 11, respectively), whereas alpha(1 sm+) mice (low expression) were normotensive (122.7 +/- 2.5 vs. 117.4 +/- 2.3; n = 11 or 12). alpha(2 sm+) Aorta, but not alpha(1 sm+) aorta, relaxed faster from a KCl-induced contraction than wild-type aorta. Our results show that smooth muscle displays unique coordinate expression of the alpha-isoforms. Increasing smooth muscle NKA decreases blood pressure and is dependent on the degree of increased alpha-isoform expression.
Authors:
Tracy J Pritchard; Michelle Parvatiyar; Daniel P Bullard; Ronald M Lynch; John N Lorenz; Richard J Paul
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-04-27
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  293     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-08-03     Completed Date:  2007-09-18     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1172-82     Citation Subset:  IM    
Affiliation:
Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0576, USA.
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MeSH Terms
Descriptor/Qualifier:
Actins / genetics
Animals
Aorta / drug effects,  enzymology,  physiopathology
Blood Pressure* / drug effects
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Hypotension / enzymology*,  physiopathology
Kinetics
Mice
Mice, Transgenic
Muscle, Smooth, Vascular / drug effects,  enzymology*
Ouabain / pharmacology
Phenylephrine / pharmacology
Potassium Chloride / pharmacology
Promoter Regions, Genetic
Pyloric Antrum / enzymology
RNA, Messenger / metabolism
Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors,  genetics,  metabolism*
Up-Regulation
Vasoconstriction* / drug effects
Vasoconstrictor Agents / pharmacology
Grant Support
ID/Acronym/Agency:
HL66044/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Actins; 0/Enzyme Inhibitors; 0/RNA, Messenger; 0/Vasoconstrictor Agents; 59-42-7/Phenylephrine; 630-60-4/Ouabain; 7447-40-7/Potassium Chloride; EC 3.6.1.-/Atp1a1 protein, rat; EC 3.6.1.-/Atp1a2 protein, rat; EC 3.6.3.9/Sodium-Potassium-Exchanging ATPase

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