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Regulation of blood pressure, natriuresis and renal thiazide/amiloride sensitivity in PPARalpha null mice.

Abstract
This study evaluated the role of PPARalpha in renal function and whether PPARalpha knockout (KO) mice are hypertensive or salt-sensitive. We hypothesize that PPARalpha modulation of ion transport defines the capacity for sodium excretion (U(Na)V). PPARalpha KO and wild-type (WT) mice were placed on a normal salt (NS, 0.5% NaCl) or high salt (8% NaCl, HS) diet for 28 days and mean arterial blood pressure (MABP) and heart rate (HR) determined. In a group of anesthetized animals on NS diet, pressure natriuresis (P/N) was determined and in another group, acute sodium load (0.9% NaCl) was administered and U(Na)V compared in mice pretreated with amiloride (200 microg/kg) or hydrochlorothiazide (3 mg/kg), in vivo measurements of sodium hydrogen exchanger or Na-Cl-cotransporter activity, respectively. MABP and HR were similar in PPARalpha KO and WT mice placed on a NS diet (116+/-6 mmHg, 587+/-40 beats/min, KO; 116+/-4 mmHg, 551+/-20 beats/min, WT). HS diet increased MABP to a greater extent in KO mice (Delta = 29+/-3 vs 14+/-3 mmHg, p<0.05) as did proteinuria (8- vs 2.5-fold, p<0.05). P/N was blunted in untreated KO mice. In response to an acute NaCl-load, U(Na)V was faster in PPARalpha KO mice (4.31+/-1.11 vs 0.77+/-0.31 micromol, p<0.05). However, U(Na)V was unchanged in hydrochlorothiazide-treated KO mice but increased 6.9-fold in WT mice. Similarly, U(Na)V was less in amiloride-treated KO mice (3.4- vs 15.5-fold). These data suggest that PPARalpha participates in pressure natriuresis and affects Na transport via amiloride- and thiazide-sensitive mechanisms. Thus, despite defective fatty acid oxidation, PPARalpha null mice are not hypertensive but develop salt-sensitive hypertension.
AuthorsPatience Obih, Adebayo O Oyekan
JournalBlood pressure (Blood Press) Vol. 17 Issue 1 Pg. 55-63 ( 2008) ISSN: 0803-7051 [Print] England
PMID18568693 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Diuretics
  • PPAR alpha
  • Sodium Chloride, Dietary
  • Thiazides
  • Sodium Chloride
  • Amiloride
Topics
  • Amiloride (therapeutic use)
  • Animals
  • Blood Pressure (drug effects, genetics)
  • Body Weight (drug effects)
  • Diuretics (therapeutic use)
  • Drug Resistance (genetics)
  • Hypertension, Renal (drug therapy, genetics, physiopathology)
  • Kidney Function Tests (methods)
  • Male
  • Mice
  • Mice, Knockout
  • Natriuresis (drug effects, genetics)
  • Organ Size (drug effects)
  • PPAR alpha (deficiency, genetics)
  • Sodium Chloride (administration & dosage, urine)
  • Sodium Chloride, Dietary
  • Thiazides (therapeutic use)

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