title: Ginsenosides block HIV protease inhibitor ritonavir-induced vascular dysfunction of porcine coronary arteries.
abstract: Human immunodeficiency virus (HIV) protease inhibitor ritonavir (RTV) may induce vascular dysfunction through oxidative stress. Ginsenosides have been shown to have potential benefits on the cardiovascular system through diverse mechanisms, including antioxidative property. The objective of this study was to determine whether ginsenosides could prevent coronary arteries from RTV-induced dysfunction. Porcine coronary artery rings were incubated with RTV and ginsenosides Rb1, Rc, and Re for 24 h. Vasomotor function was recorded by a myograph tension system. In response to the thromboxane A(2) analog U-46619, the contraction of the vessel rings was significantly reduced. When cocultured with Rb1, Rc, and Re, the contractility significantly increased. In response to bradykinin at 10(-5) M, the endothelium-dependent relaxation of vessel rings was significantly reduced by 59% for RTV compared with controls (P < 0.05). When cocultured with Rb1, Rc, and Re, the relaxation significantly increased 100%, 90%, and 134%, respectively, compared with the RTV-alone groups (P > 0.05). In response to sodium nitroprusside, RTV significantly reduced vasorelaxation. In addition, the endothelial nitric oxide synthase (eNOS) mRNA levels were significantly reduced by 78% for RTV group (P < 0.05) by real-time PCR analysis. The eNOS protein levels measured by Western blot analysis and nitrite concentrations measured by Griess assay were also decreased, whereas O(2)(-) production by lucigenin-enhanced chemiluminescence was significantly increased in the RTV-treated group. These effects of RTV were effectively blocked by ginsenosides. Thus HIV protease inhibitor RTV significantly impaired the vasomotor function of porcine coronary arteries. This effect may be mediated by the downregulation of eNOS and overproduction of O(2)(-). These results suggest that ginsenosides can effectively block RTV-induced vascular dysfunction.
authors.affiliation: Michael E. DeBakey Dept. of Surgery, One Baylor Plaza, NAB-2010, Houston, TX 77030, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Chai
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Peter
authors.initials: P
authors.lastname: Lin
authors.forename: Alan
authors.initials: A
authors.lastname: Lumsden
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Yao
authors.forename: Changyi
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D001483:Base Sequence; D001920:Bradykinin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D017931:DNA Primers; D036145:Ginsenosides / Q000494:pharmacology*; D017320:HIV Protease Inhibitors / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D023421:Models, Animal; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D016133:Polymerase Chain Reaction; D019438:Ritonavir / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D017931:DNA Primers; D036145:Ginsenosides; D017320:HIV Protease Inhibitors; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D019438:Ritonavir; D001920:Bradykinin