Salt sensitivity of blood pressure in NKCC1-deficient mice

• Published in: American Journal of Physiology - Renal Physiology 2008-10, Vol.295 (4), p.F1230-F1238
• Main Authors: Kim, Soo Mi, Eisner, Christoph, Faulhaber-Walter, Robert, Mizel, Diane, Wall, Susan M, Briggs, Josephine P, Schnermann, Jurgen
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Agonists - pharmacology; Aldosterone - blood; Animals; Antihypertensive Agents - pharmacology; Blood pressure; Blood Pressure - physiology; Circadian Rhythm - physiology; Diet; Female; Gene expression; Heart rate; 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; Physiology; Proteins; Renin - blood; Rodents; Salt; Sodium Chloride, Dietary - pharmacology; Sodium-Potassium-Chloride Symporters - genetics; Sodium-Potassium-Chloride Symporters - metabolism; Solute Carrier Family 12, Member 2; Telemetry
• ISSN: 1931-857X; 0363-6127; 1522-1466
• DOI: 10.1152/ajprenal.90392.2008

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 I.ml(-1).h(-1)) 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.