Statins as coronary vasodilators in isolated bovine coronary arteries--involvement of PGI2 and NO.
Here we studied direct vasodilation induced by statins in isolated bovine coronary arteries. In rings of coronary bovine arteries preconstricted with prostaglandin F(2 alpha) (3 x 10(-8) - 10(-5)), lovastatin, simvastatin, atorvastatin and cerivastatin (3-30 microM) but not pravastatin induced concentration-dependent vasodilation. Removal of endothelium diminished response to simvastatin, cerivastatin and atorvastatin (30 microM) (67.4+/-4.56 vs. 22.7+/-8.14%, 96.9+/-2.27% vs. 54.5+/-6.86%, 67.4+/-4.01% vs. 34.6+/-5.66%, respectively). In presence of L-NAME (300 microM) or indomethacin (5 microM) responses to simvastatin, atorvastatin and cerivastatin, were also partially diminished. In contrast, lovastatin-induced vasorelaxation was not significantly affected by removal of endothelium (35.6+/-4.19% vs. 28.8+/-5.24%) or by pretreatment with L-NAME or indomethacin. In summary, with the exception of pravastatin, statins act as coronary vasodilators. Simvastatin, cerivastatin and atorvastatin but not lovastatin induced vasodilation displayed endothelium dependent- and endothelium-independent components. The endothelium-dependent effect of statins was mediated by NO and PGI(2), while the mechanism of smooth muscle cells-dependent component remains to be determined.
Lorkowska
Barbara
B
Department of Experimental Pharmacology, Jagiellonian University School of Medicine, ul. Grzegorzecka 16, 31-531 Kraków, Poland.
Chlopicki
Stefan
S
D000818:Animals; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D011464:Epoprostenol / Q000502:physiology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D011464:Epoprostenol