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

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 (UNaV). 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 UNaV 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 protein...