Original Article

Effect of pravastatin on impaired endothelium-dependent relaxation induced by lysophosphatidylcholine in rat aorta1

Hua-fei DENG, Yan XIONG


Aim: To investigate the effects of pravastatin, a potent 3-hydroxy-3-methylglutaryl
coenzyme A (HMG-CoA) reductase inhibitor, on impaired endothelium-dependent
relaxation induced by lysophosphatidylcholine (LPC), the major component
of oxidized low-density lipoprotein, in rat thoracic aorta.
Methods: Both the
endothelium-dependent relaxation response to acetylcholine and the endotheliumindependent
relaxation response to sodium nitroprusside of aortic rings were
measured by recording isometric tension after the rings were exposed to LPC in
the absence or presence of pravastatin to estimate the injury effect of LPC and the
protective effect of pravastatin on the aortic endothelium, respectively.
Exposure of aortic rings to LPC (1–10 μmol/L) for 30 min induced a significant
concentration-dependent inhibition of endothelium-dependent relaxation to
acetylcholine, but did not affect endothelium-independent relaxation in response
to sodium nitroprusside. Pre-incubation of aortic rings with pravastatin (0.3-3
mmol/L) for 15 min and then co-incubation of the rings with LPC (3 μmol/L) for
another 30 min significantly attenuated the inhibition of endothelium-dependent
relaxation induced by LPC. This protective effect of pravastatin (1 mmol/L) was
abolished by NG-nitro-L-arginine methyl ester (30 μmol/L), an inhibitor of nitric
oxide synthase, but not by indomethacin (10 μmol/L), an inhibitor of cyclooxygenase.
Moreover, protein kinase C inhibitor chelerythrine (1 μmol/L) the
superoxide anion scavenger superoxide dismutase (200 kU/L), and the nitric oxide
precursor L-arginine (3 mmol/L) also improved the impaired endotheliumdependent
relaxation induced by LPC, similar to the effects of pravastatin.
Conclusion: Pravastatin can protect the endothelium against functional injury
induced by LPC in rat aorta, a fact which is related to increasing nitric oxide