TY - JOUR
T1 - Curcumin blocks HIV protease inhibitor ritonavir-induced vascular dysfunction in porcine coronary arteries
AU - Chai, Hong
AU - Yan, Shaoyu
AU - Lin, Peter
AU - Lumsden, Alan B.
AU - Yao, Qizhi
AU - Chen, Changyi
N1 - Funding Information:
This work is partially supported by research grants from the National Institutes of Health (Chen: R01 HL61943, R01 HL60135, R01 HL65916, R01 HL72716, and R01 EB-002436; Yao: R21 AI 49116 and R01 DE15543; Lumsden: R01 HL75824; and Lin: K08 HL076345).
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/6
Y1 - 2005/6
N2 - 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. STUDY DESIGN: Artery rings were incubated with 15 μM concentration of RTV and curcumin (5 or 10 μM) 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.
AB - 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. STUDY DESIGN: Artery rings were incubated with 15 μM concentration of RTV and curcumin (5 or 10 μM) 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.
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U2 - 10.1016/j.jamcollsurg.2005.02.030
DO - 10.1016/j.jamcollsurg.2005.02.030
M3 - Article
C2 - 15922191
AN - SCOPUS:19744369696
VL - 200
SP - 820
EP - 830
JO - Journal of the American College of Surgeons
JF - Journal of the American College of Surgeons
SN - 1072-7515
IS - 6
ER -