Abstract
Peroxisome proliferator-activated receptor-alpha (PPAR-) activation by fenofibrate reduces blood pressure and sodium retention during DOCA-salt hypertension. PPAR- 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 DOCA-salt hypertension. We performed uni-nephrectomy on 1214 week old male Swiss Webster mice and implanted biotelemetry devices in control, DOCA-salt (1.5mg/g) treated mice with or without fenofibrate (500mg/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- 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- activation protects the kidney against renal injury via decreased COX-2 expression.
| Original language | English (US) |
|---|---|
| Article number | 502631 |
| Journal | PPAR Research |
| DOIs | |
| State | Published - Dec 1 2011 |
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ASJC Scopus subject areas
- Drug Discovery
- Pharmacology (medical)
Cite this
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. / Lee, Dexter L.; Wilson, Justin L.; Duan, Rong; Hudson, Tamaro; El-Marakby, Ahmed.
In: PPAR Research, 01.12.2011.Research output: Contribution to journal › Article
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TY - JOUR
T1 - 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
AU - Lee, Dexter L.
AU - Wilson, Justin L.
AU - Duan, Rong
AU - Hudson, Tamaro
AU - El-Marakby, Ahmed
PY - 2011/12/1
Y1 - 2011/12/1
N2 - Peroxisome proliferator-activated receptor-alpha (PPAR-) activation by fenofibrate reduces blood pressure and sodium retention during DOCA-salt hypertension. PPAR- 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 DOCA-salt hypertension. We performed uni-nephrectomy on 1214 week old male Swiss Webster mice and implanted biotelemetry devices in control, DOCA-salt (1.5mg/g) treated mice with or without fenofibrate (500mg/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- 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- activation protects the kidney against renal injury via decreased COX-2 expression.
AB - Peroxisome proliferator-activated receptor-alpha (PPAR-) activation by fenofibrate reduces blood pressure and sodium retention during DOCA-salt hypertension. PPAR- 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 DOCA-salt hypertension. We performed uni-nephrectomy on 1214 week old male Swiss Webster mice and implanted biotelemetry devices in control, DOCA-salt (1.5mg/g) treated mice with or without fenofibrate (500mg/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- 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- activation protects the kidney against renal injury via decreased COX-2 expression.
UR - http://www.scopus.com/inward/record.url?scp=84862917714&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862917714&partnerID=8YFLogxK
U2 - 10.1155/2011/502631
DO - 10.1155/2011/502631
M3 - Article
C2 - 22190908
AN - SCOPUS:84862917714
JO - PPAR Research
JF - PPAR Research
SN - 1687-4757
M1 - 502631
ER -