Transgenic mice expressing Na+-K+-ATPase in smooth muscle decreases blood pressure

Tracy J. Pritchard, Michelle Parvatiyar, Daniel P. Bullard, Ronald M. Lynch, John N. Lorenz, Richard J. Paul

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

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 α1- or α2-isoform (α1sm+ or α2sm+ mice) driven by the smooth muscle-specific α-actin promoter SMP8. Interestingly, both α-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 α-isoform protein was increased from 1.5-fold (α1sm+ mice) to 7-fold (α2sm+ mice). The increase in total NKA α-isoform protein was accompanied by a 2.5-fold increase in NKA activity in α2sm+ gastric antrum. Immunocytochemistry of the α1- and α2-isoforms in α2sm+ aortic smooth muscle cells indicated that α-isoform distributions were similar to those shown in wild-type cells. α2sm+ Mice (high expression) were hypotensive (109.9 ± 1.6 vs. 121.3 ± 1.4 mmHg; n = 13 and 11, respectively), whereas α1sm+ mice (low expression) were normotensive (122.7 ± 2.5 vs. 117.4 ± 2.3; n = 11 or 12). α2sm+ Aorta, but not α1sm+ aorta, relaxed faster from a KCl-induced contraction than wild-type aorta. Our results show that smooth muscle displays unique coordinate expression of the α-isoforms. Increasing smooth muscle NKA decreases blood pressure and is dependent on the degree of increased α-isoform expression.

Original languageEnglish (US)
Pages (from-to)H1172-H1182
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume293
Issue number2
DOIs
StatePublished - Aug 2007

Keywords

  • Hypertension
  • Na-K-ATPase α-isoforms
  • Vascular contractility

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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