Relaxant effects of pravastatin, atorvastatin and cerivastatin on isolated rat aortic rings


Uydes-Dogan B. S., Topal G., Takir S., Alp F., Kaleli D., ÖZDEMİR O.

LIFE SCIENCES, vol.76, no.15, pp.1771-1786, 2005 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 76 Issue: 15
  • Publication Date: 2005
  • Doi Number: 10.1016/j.lfs.2004.11.002
  • Journal Name: LIFE SCIENCES
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1771-1786
  • Keywords: pravastatin, atorvastatin, cerivastatin, vascular relaxation, endothelium, mevalonate pathway, K-ATP channels, Na+-K+ ATP ase, rat aorta, COA-REDUCTASE INHIBITORS, NITRIC-OXIDE SYNTHASE, SMOOTH-MUSCLE CELLS, ENDOTHELIAL-CELLS, SIMVASTATIN, CHOLESTEROL, CA2+, INVOLVEMENT, CHANNELS, STATINS
  • Istanbul University Affiliated: Yes

Abstract

Increasing evidence suggests that statins may have pleiotropic effects on vascular wall independent of their cholesterol lowering properties. In the present study, we investigated the acute vascular effects of pravastatin, atorvastatin and cerivastatin on rat isolated aortic rings. Statins effectively and comparably relaxed the aortic rings precontracted submaximally with noradrenaline, in a concentration-dependent manner, in which a high potency was observed with cerivastatin. Endothelium removal or incubation of the aortic rings with nitric oxide synthase inhibitor L-NOARG (10(-4) M) and/or cyclooxygenase inhibitor indomethacin (10(-5) M) significantly attenuated the acute vasorelaxation induced by either of statin. Additionally, different from the other two statins, a significant reduction was observed in response to cerivastatin in the presence of K-ATP channel inhibitor, glibenclamide (10(-5) M) and Na+-K+ ATPase inhibitor, ouabain (10(-4) M). Furthermore, pretreatment of the rings with the cholesterol precursor mevalonate (10(-3) M) significantly inhibited the endothelium-mediated relaxant effects of the statins. Our findings suggest that statins could acutely modulate vascular tone importantly by endothelium-dependent and mevalonate-related pathways. (C) 2004 Elsevier Inc. All rights reserved.