title: Decreased blood pressure and vascular smooth muscle tone in mice lacking basolateral Na(+)-K(+)-2Cl(-) cotransporter.
abstract: 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.
authors.affiliation: Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, USA.
authors.forename: Jamie W
authors.initials: JW
authors.lastname: Meyer
authors.forename: Michael
authors.initials: M
authors.lastname: Flagella
authors.forename: Roy L
authors.initials: RL
authors.lastname: Sutliff
authors.forename: John N
authors.initials: JN
authors.lastname: Lorenz
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Nieman
authors.forename: Craig S
authors.initials: CS
authors.lastname: Weber
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Paul
authors.forename: Gary E
authors.initials: GE
authors.lastname: Shull
mesh_terms: D000136:Acid-Base Equilibrium / Q000502:physiology; D000450:Aldosterone / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002034:Bumetanide / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D004573:Electrolytes / Q000097:blood; D007022:Hypotension / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010641:Phenotype; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics* / Q000378:metabolism*; D064506:Solute Carrier Family 12, Member 2; D013314:Stress, Mechanical; D013623:Tail
chemical_list: D004232:Diuretics; D004573:Electrolytes; C578878:Slc12a2 protein, mouse; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D002034:Bumetanide; D000450:Aldosterone