title: Salt sensitivity of blood pressure in NKCC1-deficient mice.
abstract: 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.
authors.affiliation: National Institute of Digestive and Diabetes and Kidney Diseases, National Institutes of Health, 10 Center Dr.-MSC 1370, Bethesda, MD 20892, USA.
authors.forename: Soo Mi
authors.initials: SM
authors.lastname: Kim
authors.forename: Christoph
authors.initials: C
authors.lastname: Eisner
authors.forename: Robert
authors.initials: R
authors.lastname: Faulhaber-Walter
authors.forename: Diane
authors.initials: D
authors.lastname: Mizel
authors.forename: Susan M
authors.initials: SM
authors.lastname: Wall
authors.forename: Josephine P
authors.initials: JP
authors.lastname: Briggs
authors.forename: Jurgen
authors.initials: J
authors.lastname: Schnermann
mesh_terms: 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
chemical_list: 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