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

Justin L. Wilson, Rong Duan, Ahmed Abdelrazik Elmarakby, Abdulmohsin Alhashim, Dexter L. Lee

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13 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number645969
JournalPPAR Research
DOIs
StatePublished - Aug 17 2012

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Peroxisome Proliferator-Activated Receptors
Angiotensin II
Interleukin-6
Hypertension
Fenofibrate
Kidney
Cytochrome P-450 CYP4A
Intercellular Adhesion Molecule-1
Anti-Inflammatory Agents
Telemetry
Antihypertensive Agents
Up-Regulation
Equipment and Supplies

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology (medical)

Cite this

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abstract = "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.",
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AU - Duan, Rong

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AU - Alhashim, Abdulmohsin

AU - Lee, Dexter L.

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