Peroxisome proliferator‐activated receptor‐α Reduces Mean Arterial Pressure by Renal‐Dependent Mechanisms during a Slow Pressor Dose of Angiotensin II

Abstract

Peroxisome proliferator‐activated receptor‐α (PPAR‐α) activation reduces blood pressure in some hypertensive models by unclear mechanisms. We tested the hypothesis that the deletion of PPAR‐α would potentiate the slow pressor response to prolonged AngII infusion by a renal‐ dependent mechanism. We tested this hypothesis in PPAR‐α knockout (KO) and wild‐type (WT) male mice infused with AngII (400 ng/kg/min) and fed a normal salt diet for 14 days. Male KO and WT mice were implanted with biotelemetry devices and placed in metabolic cages to measure mean arterial pressure (MAP), heart rate (HR) and collect metabolic data. Male KO mice had normal basal MAP, HR and locomotor activity, sodium excretion, water intake and urine volume compared to WT, suggesting that PPAR‐α has no effect on basal MAP, HR, activity, sodium excretion, water intake and urine volume. On day 12 of AngII infusion, MAP and HR were lower in WT compared to KO mice: (MAP: 105 ± 4 vs 120 ± 3 mmHg, p < 0.001; HR: 395 ± 20 vs 500 ± 50 bpm, p < 0.001). Sodium excretion averaged 1.0 ± 0.5 and 0.8 ± 0.4 meq sodium/2 days in WT and KO, respectively, despite similar sodium intakes. Renal blood flow on day 12 of AngII was increased in WT (9.6 ± 2.3 ml/min/g) when compared to KO (7.0 ± 2.0 ml/min/g). The results suggest that during a slow pressor response to prolonged AngII infusion, the presence of PPAR‐α attenuates MAP via decreased renal vasoconstriction and increased sodium excretion.