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Am J Physiol Heart Circ Physiol (July 11, 2002). doi:10.1152/ajpheart.00083.2002
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Articles in PresS, published online ahead of print July 11, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00083.2002
Submitted on January 31, 2002
Accepted on July 3, 2002

Decreased blood pressure and vascular smooth muscle tone in mice lacking basolateral Na-K-2Cl cotransporter

Jamie W. Meyer1, Michael Flagella1, Roy L. Sutliff2, John N. Lorenz3, Michelle L. Nieman3, Craig S. Weber3, Richard J. Paul3, and Gary E. Shull1*

1 Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
2 Pathology, Emory University, Atlanta, Georgia, USA; Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
3 Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

* To whom correspondence should be addressed. E-mail: shullge{at}ucmail.uc.edu.

The basolateral Na-K-2Cl cotransporter (NKCC1) functions in the maintenance of cellular electrolyte and volume homeostasis. NKCC1-deficient (Nkcc1-/-) mice were used to examine its role in cardiac function and in the maintenance of blood pressure and vascular tone. Tail-cuff measurements demonstrated that awake Nkcc1-/- mice had significantly lower systolic blood pressure than wild-type mice (114.5±2.2 and 131.8±2.5 mm Hg, respectively). Serum aldosterone levels were normal, indicating that extracellular fluid-volume homeostasis was not impaired. Studies using pressure transducers in the femoral artery and left ventricle showed that anesthetized Nkcc1-/- mice have decreased mean arterial pressure and left ventricular pressure, while myocardial contraction parameters were not significantly different from those of wild-type mice. When stimulated with phenylephrine, aortic smooth muscle from wild-type and Nkcc1-/- mice exhibited no significant differences in maximum contractility and only moderate dose-response shifts. In phasic portal vein smooth muscle from Nkcc1-/- mice, a sharp reduction in mechanical force was noted. These results indicate that NKCC1 can be important for the maintenance of normal blood pressure and vascular tone.




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