Salt sensitivity of blood pressure in NKCC1-deficient mice

Am J Physiol Renal Physiol. 2008 Oct;295(4):F1230-8. doi: 10.1152/ajprenal.90392.2008. Epub 2008 Aug 13.


NKCC1 is a widely expressed isoform of the Na-2Cl-K cotransporter that mediates several direct and indirect vascular effects and regulates expression and release of renin. In this study, we used NKCC1-deficient (NKCC1-/-) and wild-type (WT) mice to assess day/night differences of blood pressure (BP), locomotor activity, and renin release and to study the effects of high (8%) or low (0.03%) dietary NaCl intake on BP, activity, and the renin/aldosterone system. On a standard diet, 24-h mean arterial blood pressure (MAP) and heart rate determined by radiotelemetry, and their day/night differences, were not different in NKCC1-/- and WT mice. Spontaneous and wheel-running activities in the active night phase were lower in NKCC1-/- than WT mice. In NKCC1-/- mice on a high-NaCl diet, MAP increased by 10 mmHg in the night without changes in heart rate. In contrast, there was no salt-dependent blood pressure change in WT mice. MAP reductions by hydralazine (1 mg/kg) or isoproterenol (10 microg/mouse) were significantly greater in NKCC1-/- than WT mice. Plasma renin (PRC; ng ANG and aldosterone (aldo; pg/ml) concentrations were higher in NKCC1-/- than WT mice (PRC: 3,745+/-377 vs. 1,245+/-364; aldo: 763+/-136 vs. 327+/-98). Hyperreninism and hyperaldosteronism were found in NKCC1-/- mice during both day and night. High Na suppressed PRC and aldosterone in both NKCC1-/- and WT mice, whereas a low-Na diet increased PRC and aldosterone in WT but not NKCC1-/- mice. We conclude that 24-h MAP and MAP circadian rhythms do not differ between NKCC1-/- and WT mice on a standard diet, probably reflecting a balance between anti- and prohypertensive factors, but that blood pressure of NKCC1-/- mice is more sensitive to increases and decreases of Na intake.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Aldosterone / blood
  • Animals
  • Antihypertensive Agents / pharmacology
  • Blood Pressure / physiology*
  • Circadian Rhythm / physiology
  • Female
  • Heart Rate / physiology
  • Homeostasis / drug effects
  • Homeostasis / physiology
  • Hydralazine / pharmacology
  • Hypertension, Renal / drug therapy
  • Hypertension, Renal / physiopathology*
  • Isoproterenol / pharmacology
  • Male
  • Mice
  • Mice, Mutant Strains
  • Monitoring, Physiologic
  • Motor Activity / physiology
  • Renin / blood
  • Sodium Chloride, Dietary / pharmacology*
  • Sodium-Potassium-Chloride Symporters / genetics*
  • Sodium-Potassium-Chloride Symporters / metabolism*
  • Solute Carrier Family 12, Member 2
  • Telemetry


  • Adrenergic beta-Agonists
  • Antihypertensive Agents
  • Slc12a2 protein, mouse
  • Sodium Chloride, Dietary
  • Sodium-Potassium-Chloride Symporters
  • Solute Carrier Family 12, Member 2
  • Hydralazine
  • Aldosterone
  • Renin
  • Isoproterenol