Salt sensitivity of blood pressure in NKCC1-deficient mice.
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.
Kim
Soo Mi
SM
National Institute of Digestive and Diabetes and Kidney Diseases, National Institutes of Health, 10 Center Dr.-MSC 1370, Bethesda, MD 20892, USA.
Eisner
Christoph
C
Faulhaber-Walter
Robert
R
Mizel
Diane
D
Wall
Susan M
SM
Briggs
Josephine P
JP
Schnermann
Jurgen
J
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000450:Aldosterone / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006830:Hydralazine / Q000494:pharmacology; D006977:Hypertension, Renal / Q000188:drug therapy / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008991:Monitoring, Physiologic; D009043:Motor Activity / Q000502:physiology; D012083:Renin / Q000097:blood; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics* / Q000378:metabolism*; D064506:Solute Carrier Family 12, Member 2; D013686:Telemetry
D000318:Adrenergic beta-Agonists; D000959:Antihypertensive Agents; C578878:Slc12a2 protein, mouse; D017673:Sodium Chloride, Dietary; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D006830:Hydralazine; D000450:Aldosterone; D012083:Renin; D007545:Isoproterenol