Peroxisome Proliferator-Activated Receptor-α Activation Decreases Mean Arterial Pressure, Plasma Interleukin-6, and COX-2 While Increasing Renal CYP4A Expression in an Acute Model of DOCA-Salt Hypertension

Hdl Handle:
http://hdl.handle.net/10675.2/770
Title:
Peroxisome Proliferator-Activated Receptor-α Activation Decreases Mean Arterial Pressure, Plasma Interleukin-6, and COX-2 While Increasing Renal CYP4A Expression in an Acute Model of DOCA-Salt Hypertension
Authors:
Lee, Dexter L.; Wilson, Justin L.; Duan, Rong; Hudson, Tamaro ( 0000-0002-1660-1121 ) ; El-Marakby, Ahmed
Abstract:
Peroxisome proliferator-activated receptor-alpha (PPAR-α) activation by fenofibrate reduces blood pressure and sodium retention during DOCA-salt hypertension. PPAR-α activation reduces the expression of inflammatory cytokines, such as interleukin- 6 (IL-6). Fenofibrate also induces cytochrome P450 4A (CYP4A) and increases 20-hydroxyeicosatetraenoic acid (20-HETE) production. This study tested whether the administration of fenofibrate would reduce blood pressure by attenuating plasma IL-6 and renal expression of cyclooxygenase-2 (COX-2), while increasing expression of renal CYP4A during 7 days of DOCAsalt hypertension. We performed uni-nephrectomy on 12–14 week old male Swiss Webster mice and implanted biotelemetry devices in control, DOCA-salt (1.5mg/g) treated mice with or without fenofibrate (500 mg/kg/day in corn oil, intragastrically). Fenofibrate significantly decreased mean arterial pressure and plasma IL-6. In kidney homogenates, fenofibrate increased CYP4A and decreased COX-2 expression. There were no differences in renal cytochrome P450, family 2, subfamily c, polypeptide 23 (CYP2C23) and soluble expoxide hydrolase (sEH) expression between the groups. Our results suggest that the blood pressure lowering effect of PPAR-α activation by fenofibrate involves the reduction of plasma IL-6 and COX-2, while increasing CYP4A expression during DOCA-salt hypertension. Our results may also suggest that PPAR-α activation protects the kidney against renal injury via decreased COX-2 expression.
Citation:
PPAR Res. 2011 Dec 7; 2011:502631
Issue Date:
7-Dec-2011
URI:
http://hdl.handle.net/10675.2/770
DOI:
10.1155/2011/502631
PubMed ID:
22190908
PubMed Central ID:
PMC3236317
Type:
Article
ISSN:
1687-4765
Appears in Collections:
Department of Oral Biology: Faculty Research and Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorLee, Dexter L.en_US
dc.contributor.authorWilson, Justin L.en_US
dc.contributor.authorDuan, Rongen_US
dc.contributor.authorHudson, Tamaroen_US
dc.contributor.authorEl-Marakby, Ahmeden_US
dc.date.accessioned2012-10-26T20:30:41Z-
dc.date.available2012-10-26T20:30:41Z-
dc.date.issued2011-12-07en_US
dc.identifier.citationPPAR Res. 2011 Dec 7; 2011:502631en_US
dc.identifier.issn1687-4765en_US
dc.identifier.pmid22190908en_US
dc.identifier.doi10.1155/2011/502631en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/770-
dc.description.abstractPeroxisome proliferator-activated receptor-alpha (PPAR-α) activation by fenofibrate reduces blood pressure and sodium retention during DOCA-salt hypertension. PPAR-α activation reduces the expression of inflammatory cytokines, such as interleukin- 6 (IL-6). Fenofibrate also induces cytochrome P450 4A (CYP4A) and increases 20-hydroxyeicosatetraenoic acid (20-HETE) production. This study tested whether the administration of fenofibrate would reduce blood pressure by attenuating plasma IL-6 and renal expression of cyclooxygenase-2 (COX-2), while increasing expression of renal CYP4A during 7 days of DOCAsalt hypertension. We performed uni-nephrectomy on 12–14 week old male Swiss Webster mice and implanted biotelemetry devices in control, DOCA-salt (1.5mg/g) treated mice with or without fenofibrate (500 mg/kg/day in corn oil, intragastrically). Fenofibrate significantly decreased mean arterial pressure and plasma IL-6. In kidney homogenates, fenofibrate increased CYP4A and decreased COX-2 expression. There were no differences in renal cytochrome P450, family 2, subfamily c, polypeptide 23 (CYP2C23) and soluble expoxide hydrolase (sEH) expression between the groups. Our results suggest that the blood pressure lowering effect of PPAR-α activation by fenofibrate involves the reduction of plasma IL-6 and COX-2, while increasing CYP4A expression during DOCA-salt hypertension. Our results may also suggest that PPAR-α activation protects the kidney against renal injury via decreased COX-2 expression.en_US
dc.rightsCopyright © 2011 Dexter L. Lee et al.en_US
dc.subjectResearch Articleen_US
dc.titlePeroxisome Proliferator-Activated Receptor-α Activation Decreases Mean Arterial Pressure, Plasma Interleukin-6, and COX-2 While Increasing Renal CYP4A Expression in an Acute Model of DOCA-Salt Hypertensionen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3236317en_US
dc.contributor.corporatenameDepartment of Oral Biology-
dc.contributor.corporatenameDepartment of Pharmacology and Toxicology-
All Items in Scholarly Commons are protected by copyright, with all rights reserved, unless otherwise indicated.