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Am J Physiol Heart Circ Physiol 283: H1846-H1855, 2002. First published July 11, 2002; doi:10.1152/ajpheart.00083.2002
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Vol. 283, Issue 5, H1846-H1855, November 2002

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

Jamie W. Meyer1, Michael Flagella1, Roy L. Sutliff2, John N. Lorenz2, Michelle L. Nieman2, Craig S. Weber2, Richard J. Paul2, and Gary E. Shull1

Departments of 1 Molecular Genetics, Biochemistry, and Microbiology and 2 Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267

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 (Nkcc1+/+) mice (114.5 ± 2.2 and 131.8 ± 2.5 mmHg, 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, whereas myocardial contraction parameters were not significantly different from those of Nkcc1+/+ mice. When stimulated with phenylephrine, aortic smooth muscle from Nkcc1+/+ 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, however, 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.

vasculature; hypotension; bumetanide


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