Study on the beneficial effect of dual peroxisome proliferator-activated receptor agonist WY14643 on vascular endothelium

Abstract

Objective The 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.Methods Isometric 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.Results Compared 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).Conclusions Those data showed that WY14643 reduced the release of EDCFs,it suggests that WY14643 protects against vascular diseases through the PPAR activators in spontaneous hypertension. Key words: Peroxisome proliferator-activated receptors/agonists; Cyclooxygenase 1/metabolism; Endothelins/metabolism; Hypertension; Rats