Peroxisome proliferator activated receptor- agonist slows the progression of hypertension, attenuates plasma interleukin-6 levels and renal inflammatory markers in angiotensin II infused mice

The anti-inflammatory properties of PPAR-α plays an important role in attenuating hypertension. The current study determines the anti-hypertensive and anti-inflammatory role of PPAR- agonist during a slow-pressor dose of Ang II (400ng/kg/min). Ten to twelve week old male PPAR- KO mice and their WT controls were implanted with telemetry devices and infused with Ang II for 12 days. On day 12 of Ang II infusion, MAP was elevated in PPAR- KO mice compared to WT (161 4 mmHg versus 145 ± 4 mmHg) and fenofibrate (145mg/kg/day) reduced MAP in WT + Ang II mice (134 ± 7 mmHg). Plasma IL-6 levels were higher in PPAR- KO mice on day 12 of Ang II infusion (30 ± 4 versus 8 ± 2 pg/mL) and fenofibrate reduced plasma IL-6 in Ang II-treated WT mice (10 ± 3 pg/mL). Fenofibrate increased renal expression of CYP4A, restored renal CYP2J expression, reduced the elevation in renal ICAM-1, MCP-1 and COX-2 in WT + Ang II mice. Our results demonstrate that activation of PPAR- attenuates Ang II-induced hypertension through up-regulation of CYP4A and CYP2J and an attenuation of inflammatory markers such as plasma IL-6, renal MCP-1, renal expression of ICAM-1 and COX-2.