Study on the beneficial effect of dual peroxisome proliferator-activated receptor agonist WY14643 on vascular endothelium
10.3760/cma.j.issn.1008-1372.2012.06.008
- VernacularTitle:过氧化物酶体增殖物激活受体双重激动剂WY14643对血管内皮的保护研究
- Author:
Chen QU
;
Liang TANG
;
Yan ZHU
- Publication Type:Journal Article
- Keywords:
Peroxisome proliferator-activated receptors/agonists;
Cyclooxygenase 1/metabolism;
Endothelins/metabolism;
Hypertension;
Rats
- From:
Journal of Chinese Physician
2012;14(6):746-749
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveThe present study aimed to determine whether or not dual paroxysm proliferator-activated receptor (PPAR) agonist,WY14643,improved the dysfunctioned vascular endothelium in hypertension by reducing endothelium-derived contracting factors ( EDCFs ),and to explore the molecular mechanism it was involved in.MethodsIsometric tension in isolated thoracic aortic rings of spontaneously hypertensive rats was recorded.Endothelium-dependent contractions evoked by acetylcholine in the presence of L NAME were reduced by fenofibrate.Cyclooxygenase 1 ( COX1 ) activities were determined by analyzing the peroxidase activity of cyclooxygenase colorimetrically by using ELISA kit.ResultsCompared to the control group,WY14643 significantly decreased the vasoconstriction in aorta of the SHR rats(P=0.014).PPARα antagonist MK866 enhanced the vascular contractility of SHR rats that were incubated with 10.0μmol/L WY14643( P=0.021 ).PPARΥ antagonist GW9662 did not significantly affect the vascular contractility of SHR rats that were incubated with 10.0 μmol/L WY14643( P=0.061 ).The levels of serum PGFlα(P=0.012),2α( P =0.019) and TXB2(P=0.023) in SHR rats incubated with 10.0 μmol/L WY14643 were significantly lower than the control group,respectively.Under the condition of the existence of vascular endothelium,the expression of COX-1 in SHR rats incubated with WY14643 was significantly lower than that in SHR rats incubated without WY14643 (P=0.017).ConclusionsThose data showed that WY14643 reduced the release of EDCFs,it suggests that WY14643 protects against vascular diseases through the PPAR activators in spontaneous hypertension.
