Anti-Hypertensive Action of Fenofibrate via UCP2 Upregulation Mediated by PPAR Activation in Baroreflex Afferent Pathway.
10.1007/s12264-018-0271-1
- Author:
Jian GUAN
1
;
Miao ZHAO
1
;
Chao HE
1
;
Xue LI
1
;
Ying LI
1
;
Jie SUN
1
;
Wei WANG
1
;
Ya-Li CUI
1
;
Qing ZHANG
1
;
Bai-Yan LI
2
;
Guo-Fen QIAO
3
Author Information
1. Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China.
2. Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China. liby@ems.hrbmu.edu.cn.
3. Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China. qiaogf88@163.com.
- Publication Type:Journal Article
- Keywords:
Baroreflex afferent function;
Blood pressure regulation;
Fenofibrate;
Mitochondrial uncoupling protein;
Peroxisome proliferator-activated receptor
- MeSH:
Afferent Pathways;
drug effects;
Animals;
Antihypertensive Agents;
pharmacology;
Baroreflex;
drug effects;
Blood Pressure;
drug effects;
Fenofibrate;
pharmacology;
Male;
Oxidative Stress;
drug effects;
PPAR gamma;
drug effects;
metabolism;
Rats, Sprague-Dawley;
Signal Transduction;
drug effects;
Transcriptional Activation;
drug effects;
Uncoupling Protein 2;
drug effects;
metabolism;
Up-Regulation
- From:
Neuroscience Bulletin
2019;35(1):15-24
- CountryChina
- Language:English
-
Abstract:
Fenofibrate, an agonist for peroxisome proliferator-activated receptor alpha (PPAR-α), lowers blood pressure, but whether this action is mediated via baroreflex afferents has not been elucidated. In this study, the distribution of PPAR-α and PPAR-γ was assessed in the nodose ganglion (NG) and the nucleus of the solitary tract (NTS). Hypertension induced by drinking high fructose (HFD) was reduced, along with complete restoration of impaired baroreceptor sensitivity, by chronic treatment with fenofibrate. The molecular data also showed that both PPAR-α and PPAR-γ were dramatically up-regulated in the NG and NTS of the HFD group. Expression of the downstream signaling molecule of PPAR-α, the mitochondrial uncoupling protein 2 (UCP2), was up-regulated in the baroreflex afferent pathway under similar experimental conditions, along with amelioration of reduced superoxide dismutase activity and increased superoxide in HFD rats. These results suggest that chronic treatment with fenofibrate plays a crucial role in the neural control of blood pressure by improving baroreflex afferent function due at least partially to PPAR-mediated up-regulation of UCP2 expression and reduction of oxidative stress.
