title: Molecular mechanism of vasorelaxant and antiatherogenic effects of the statins in the human saphenous vein graft.
abstract: In this study we aimed to investigate the vasorelaxant and antiatherogenic effects of the statins (fluvastatin and pravastatin) in the human saphenous vein grafts at the molecular level by using histopathologic, pharmacological and immunochemical techniques. The saphenous vein grafts evaluated histopathologically displayed a loss in their endothelium up to a ratio of 30% and set forth indications of functional deterioration. The pharmacological evaluations proved that the relaxation responses induced by fluvastatin and pravastatin were significantly inhibited by nitric oxide synthase inhibitor, N(G)-nitro-l-arginine, and cyclooxygenase inhibitor, indomethacin, while these responses were significantly increased by angiotensin converting enzyme inhibitors, captopril and enalapril, and rho kinase inhibitor, Y27632. The results of immunochemical studies are in accordance with the results of the pharmacological studies that the related statins increased the levels of nitric oxide, phospholipase A(2) and they decreased the levels of angiotensin II and active rho kinase. On the other hand mevalonolactone, a substrate of lipid metabolism, failed to change the effects of fluvastatin and pravastatin in the related tissue. The experimental results indicate that activation of nitric oxide synthase and phospholipase A(2)-cyclooxygenase pathway and inhibition of angiotensin converting enzyme and rho kinase may have a role on the effects of fluvastatin and pravastatin in the human saphenous vein grafts. It seems that the vasorelaxant and antiatherogenic effects of the related statins are independent of their lipid lowering mechanism.
authors.affiliation: University of Çukurova, Faculty of Medicine, Department of Pharmacology 01330 Adana, Turkey. yakdas25@cu.edu.tr
authors.forename: Naciye
authors.initials: N
authors.lastname: Yaktubay Döndaş
authors.forename: Nehir
authors.initials: N
authors.lastname: Sucu
authors.forename: Banu
authors.initials: B
authors.lastname: Coşkun Yilmaz
authors.forename: Halil Mahir
authors.initials: HM
authors.lastname: Kaplan
authors.forename: Murat
authors.initials: M
authors.lastname: Ozeren
authors.forename: Mehmet Kerem
authors.initials: MK
authors.lastname: Karaca
authors.forename: Ozden
authors.initials: O
authors.lastname: Vezir
authors.forename: Ergin
authors.initials: E
authors.lastname: Singirik
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy*; D001026:Coronary Artery Bypass; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012501:Saphenous Vein / Q000187:drug effects / Q000378:metabolism / Q000502:physiology* / Q000637:transplantation*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014665:Vasodilator Agents; D000804:Angiotensin II; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D054460:rho-Associated Kinases