Relaxant effects of pravastatin, atorvastatin and cerivastatin on isolated rat aortic rings.
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 KATP 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.
Sönmez Uydeş-Doğan
B
B
Istanbul University Faculty of Pharmacy, Department of Pharmacology, 34116, Beyazit, Istanbul, Turkey. sudogan@tr.net
Topal
Gökçe
G
Takir
Selçuk
S
Ilkay Alp
F
F
Kaleli
Deniz
D
Ozdemir
Osman
O
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D000069059:Atorvastatin; D004730:Endothelium, Vascular / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D019335:Nitroarginine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D017035:Pravastatin / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011725:Pyridines; D011758:Pyrroles; D019335:Nitroarginine; D010042:Ouabain; D000069059:Atorvastatin; C086276:cerivastatin; D017035:Pravastatin; D005905:Glyburide