Objective: To evaluate the effect of peroxisome proliferator-activated receptor (PPAR)α agonist fenofibrate on the secretion of endothelium-derived contracting factors in hypertensive rats.
Methods: The changes of vascular tension in SHR rats after having been incubated with 0.1, 1.0, or 10.0 μmol/L fenofibrate or 10.0 μmol/L fenofibrate and PPARα antagonist MK866 or PPARγ antagonist GW9662 for one hour were observed, and the findings were compared with those in WKY rats (control group). The serum levels of vascular endothelial contraction factor prostacyclin (PGF) 1α, 2α, and thromboxane B2 (TXB2) were determined by enzyme-linked immunosorbent assay (ELISA). The expression of COX-1 protein was determined by Western blot analysis.
Results: Compared with the control group, fenofibrate significantly reduced the vasoconstriction ability of the SHR rats(P=0.013). PPARα antagonist MK866 significantly improved the vascular contractility of SHR rats that had been incubated with 10.0 μmol/L fenofibrate (P=0.021). PPARγ antagonist GW9662 had no significant effect on the vascular contractility of SHR rats after having been incubated with 10.0 μmol/L fenofibrate (P=0.071). The serum levels of PGF1α(P=0.014), 2α(P=0.023), and TXB2 (P=0.017) in SHR rats incubated with 10.0 μmol/L fenofibrate were significantly lower than in the control group. With the presence of vascular endothelium, the expression of COX-1 in SHR rats incubated with fenofibrate was significantly lower than that in SHR rats incubated without fenofibrate (P=0.027).
Conclusion: Fenofibrate reduces the secretion of endothelium-dependent contracting factors in SHR rats through lowering the expression of COX-1.