PPAR‐α regulates NOX2 and SOD expression in the heart during Angiotensin II hypertension

Abstract

Previous reports suggest peroxisome proliferator‐activated receptor‐α (PPAR‐α) agonist attenuates hypertension by suppressing oxidative stress and increasing superoxide dismutase (SOD) activity. We tested the hypothesis that the absence of PPAR‐α would increase NOX2 and decrease SOD expression in mice hearts during Angiotensin II (ANG II) hypertension. Ten to twelve week old male PPAR‐α knockout (KO) mice and their wild‐type (WT) controls were implanted with biotelemetry devices and infused with ANG II (400 ng/kg/min) for twelve days. Separate groups of PPAR‐α KO and WT mice were treated with ANG II plus apocynin (1 g/1L) and ANG II + fenofibrate (500 mg/kg/day). Mean arterial pressure (MAP) and heart rates (HR) were similar between PPAR‐α KO and WT mice during the control period. On day twelve of ANG II treatment, MAP was significantly higher in PPAR‐α KO than WT, 161 ± 5 and 145 ± 4 mmHG, respectively. Fenofibrate significantly reduced MAP in ANG II treated WT mice (134 ± 5 mmHg) and apocynin reduced MAP in both ANG II treated PPAR‐α KO and WT mice. NOX2 expression was significantly increased in ANG II‐treated PPAR‐α KO mice hearts with no significant changes in ANG II‐treated WT mice. Apocynin significantly reduced NOX2 expression in ANG II‐treated PPAR‐α KO mice with no changes in WT. SOD expression in ANG II + fenofibrate was significantly higher than ANG II‐treated WT mice, with no differences between ANG II + fenofibrate and ANG II‐treated PPAR‐α KO. Our results suggest that increased NOX2 and decreased SOD expression in PPAR‐α KO mice hearts contributes to the significant increases in MAP during ANG II hypertension.