title: Effects and mechanisms of Fenofibrate on the secretion of vascular endothelial contraction factors in hypertensive rats.
abstract: This study investigated the effects of the peroxisome proliferator-activated receptor alpha (PPAR-α) agonist, Fenofibrate, on the secretion of vascular endothelial contraction factors in hypertensive rats to elucidate its possible mechanisms. The vascular ring contraction experiment was used to observe whether rat vascular tension of clean grade spontaneously hypertensive rats (SHR) changes after 1-h incubation of 0.1, 1.0, 10.0 μM Fenofibrate with 10.0 μM Fenofibrate, a PPAR-α antagonist (MK866), and a PPAR-γ antagonist (GW9662) in SHR. The results were compared with Wistar Kyoto rats. Enzyme-linked immunosorbent assay was used to detect the secretion of the serum vascular endothelial contraction factor prostacyclin-1α (PGF-1α), PGF-2α, and thromboxane B2 (TXB2). Western blot was used to detect COX-1 protein expression. A quantity of 10.0 μM Fenofibrate significantly reduced vasoconstriction in SHR compared to the control group (P = 0.013). The PPAR-α antagonist, MK866, significantly improved the vascular contractility of SHR when incubated with 10.0 μM Fenofibrate (P = 0.021). The PPAR-γ antagonist, GW9662, had no significant effect on the vascular contractility of SHR when incubated with 10.0 μM Fenofibrate (P = 0.071). The isolated aorta of SHR released significantly lower PGF- 1α (P = 0.014), PGF-2α (P = 0.023), and TXB2 (P = 0.017) levels in the 10.0 μM Fenofibrate group compared to the control group. COX-1 expression of SHR rat vascular endothelium was significantly depressed in the 10.0 μM Fenofibrate group compared to the control group (P = 0.027). In conclusion, Fenofibrate reduces the secretion of vascular endothelial contraction factors in hypertensive rats, which might arise through the endothelium influencing COX-1 expression.
authors: Department of Cardiac Surgery, General Hospital of Shenyang Military Region, Shenyang, China.
authors: Y
authors: Y
authors: Zhu
authors: Department of Cardiac Surgery, General Hospital of Shenyang Military Region, Shenyang, China zhu13309888139@163.com.
authors: H-S
authors: HS
authors: Wang
authors: Department of Cardiac Surgery, General Hospital of Shenyang Military Region, Shenyang, China.
authors: X-M
authors: XM
authors: Li
authors: Department of Cardiology, Shenyang Medical College Affiliated with Fengtian Hospital, Shenyang, China.
authors: C
authors: C
authors: Qu
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D015237:Dinoprost / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D011345:Fenofibrate / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D047493:PPAR alpha / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011460:Prostaglandins F / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013929:Thromboxane B2 / Q000378:metabolism; D046509:Tissue Culture Techniques; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D000960:Hypolipidemic Agents; D008565:Membrane Proteins; D047493:PPAR alpha; D047495:PPAR gamma; D011460:Prostaglandins F; D013929:Thromboxane B2; D015237:Dinoprost; D051545:Cyclooxygenase 1; C496513:Ptgs1 protein, rat; D011345:Fenofibrate; C100006:prostaglandin F1