Curcumin blocks HIV protease inhibitor ritonavir-induced vascular dysfunction in porcine coronary arteries.
BACKGROUND
HIV protease inhibitor ritonavir (RTV) is associated with many cardiovascular complications and causes vascular dysfunction through oxidative stress. In the present study, we determined the effects of RTV and curcumin (a pigment derived from turmeric) on porcine coronary arteries.


METHODS
Artery rings were incubated with 15 microM concentration of RTV and curcumin (5 or 10 microM) for 24 hours. Vasomotor function was studied with a myograph tension system. Endothelial nitric oxide synthase (eNOS) mRNA and protein levels were studied using real-time polymerase chain reaction, Western blot, and immunohistochemistry. Nitric oxide was measured using Griess assay. Superoxide anion levels were determined by lucigenin enhanced chemiluminescence.


RESULTS
RTV considerably reduced vessel contraction by 71%, endothelium-dependent relaxation by 59%, and endothelium-independent relaxation by 52%, as compared with controls. Curcumin effectively blocked RTV-induced vasomotor dysfunction. RTV-treated arteries showed substantial reductions of eNOS mRNA by 77%, eNOS protein by 72%, and nitric oxide release by 37% as compared with controls. The RTV plus curcumin-treated vessels showed substantial increases of eNOS and nitric oxide levels as compared with the RTV-treated vessels. Finally, there was a 47% increase of superoxide anion production in the RTV-treated vessels as compared with controls. Again, curcumin effectively reversed this effect of RTV.


CONCLUSIONS
HIV protease inhibitor RTV impairs vasomotor functions, reduces eNOS expression and nitric oxide release, and increases oxidative stress in porcine coronary arteries. Curcumin effectively blocks these detrimental effects of RTV.
Chai
Hong
H
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.
Yan
Shaoyu
S
Lin
Peter
P
Lumsden
Alan B
AB
Yao
Qizhi
Q
Chen
Changyi
C
D000818:Animals; D015153:Blotting, Western; D003331:Coronary Vessels / Q000737:chemistry / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology*; D017320:HIV Protease Inhibitors / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D009213:Myography; D009569:Nitric Oxide / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D019438:Ritonavir / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013481:Superoxides / Q000032:analysis; D013552:Swine; D014666:Vasomotor System / Q000187:drug effects*
D017320:HIV Protease Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D013481:Superoxides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D003474:Curcumin; D019438:Ritonavir