The soybean isoflavonoid equol blocks ritonavir-induced endothelial dysfunction in porcine pulmonary arteries and human pulmonary artery endothelial cells.
HIV protease inhibitor (PI) ritonavir (RTV) may cause vascular injury through oxidative stress. Our purpose in this study was to determine whether equol, a soy isoflavone, could prevent RTV-induced endothelial dysfunction in porcine pulmonary arteries and in human pulmonary artery endothelial cells (HPAEC). Fresh porcine pulmonary artery rings were treated with 15 micromol/L of RTV and/or equol in concentrations of 0.1, 1, and 10 micromol/L for 24 h. A control was set with no amount of equol or RTV administered. Based on myograph tension analysis, RTV significantly reduced endothelium-dependent relaxation in response to bradykinin in the artery rings compared with untreated vessels, whereas the antioxidant equol effectively reversed the RTV effect in a concentration-dependent manner. RTV also reduced the contraction of artery rings in response to thromboxane A(2) analogue U46619 and this reduction was blocked by equol. In addition, RTV treatment significantly reduced endothelial nitric oxide synthase (eNOS) expression in both porcine pulmonary arteries and HPAEC, whereas equol effectively blocked RTV-induced eNOS downregulation. Furthermore, RTV significantly increased superoxide anion production, whereas equol reversed this effect of RTV in porcine pulmonary arteries. Thus, the antioxidant equol effectively protects vascular function from the detrimental effects of HIV PI RTV in both porcine pulmonary arteries and HPAEC via a reduction in the vasomotor dysfunction, eNOS downregulation, and oxidative stress induced by RTV. These novel data suggest that equol may have a clinical application in preventing HIV-associated cardiovascular complications.
Cheng
Charlie
C
Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
Wang
Xinwen
X
Weakley
Sarah M
SM
Kougias
Panagiotis
P
Lin
Peter H
PH
Yao
Qizhi
Q
Chen
Changyi
C
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D042783:Endothelial Cells / Q000187:drug effects*; D060754:Equol; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D017320:HIV Protease Inhibitors / Q000009:adverse effects; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage / Q000494:pharmacology*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D048789:Phytoestrogens / Q000494:pharmacology; D011651:Pulmonary Artery / Q000166:cytology* / Q000502:physiology*; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects*; D013025:Glycine max; D013481:Superoxides / Q000378:metabolism; D013552:Swine
C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D017320:HIV Protease Inhibitors; D007529:Isoflavones; D048789:Phytoestrogens; D013481:Superoxides; D060754:Equol; D052250:Nitric Oxide Synthase Type III; D019438:Ritonavir