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

• Published in: Blood pressure Vol. 17; no. 1; pp. 55 - 63
• Main Authors: Obih, Patience, Oyekan, Adebayo O.
• Format: Journal Article
• Language: English
• Published: Taylor & Francis 01.01.2008
• Subjects: Blood pressure; PPARα; pressure natriuresis; salt-sensitive hypertension; sodium transport
• ISSN: 0803-7051; 1651-1999
• DOI: 10.1080/08037050701789278

This study evaluated the role of PPARα in renal function and whether PPARα knockout (KO) mice are hypertensive or salt-sensitive. We hypothesize that PPARα modulation of ion transport defines the capacity for sodium excretion (U Na V). PPARα 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 µg/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 PPARα 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 (Δ = 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 PPARα KO mice (4.31±1.11 vs 0.77±0.31 µmol, 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 PPARα participates in pressure natriuresis and affects Na transport via amiloride- and thiazide-sensitive mechanisms. Thus, despite defective fatty acid oxidation, PPARα null mice are not hypertensive but develop salt-sensitive hypertension.