Capsaicin blocks HIV protease inhibitor ritonavir-induced vascular dysfunction in porcine pulmonary arteries.
BACKGROUND
Highly active antiretroviral therapy (HAART) including HIV protease inhibitor ritonavir may be associated with the clinical complications including accelerated atherosclerosis and pulmonary artery hypertension. The objective of this study was to determine whether capsaicin, a major ingredient of hot pepper with antioxidative property, could effectively inhibit ritonavir-induced oxidative injury in porcine pulmonary arteries.


METHODS
Fresh porcine pulmonary artery rings were treated with ritonavir (15 microM), capsaicin (50 microM) or both for 24 hours and, then, subjected to myograph analysis in response to vasoactive drugs including thromboxane A2 analog U-46619, bradykinin, and sodium nitroprusside (SNP).


RESULTS
In response to U-46619 (3x10(-8) M), ritonavir-treated porcine pulmonary artery rings reduced the contraction by 15% compared with control rings. In response to bradykinin (10(-6) M), ritonavir-treated rings showed a significant reduction of endothelium-dependent vasorelaxation by 32% compared with untreated control vessels (P<0.05, n=5, Student t-test). However, ritonavir treatment did not change endothelium-independent vasorelaxation in response to SNP (10(-6) M). Capsaicin-treated vessel rings did not show any significant changes in response to U-46619, bradykinin, and SNP compared with untreated control vessels. More importantly, capsaicin co-cultured with ritonavir significantly blocked ritonavir-induced inhibition of endothelium-dependent vasorelaxation and contraction compared with ritonavir alone treatment in porcine pulmonary artery rings (P<0.05, n=5, Student t-test).


CONCLUSIONS
Capsaicin effectively inhibits the detrimental effects of HIV protease inhibitor ritonavir on vasomotor functions of porcine pulmonary arteries. These findings may suggest that capsaicin could have clinical applications to prevent vascular and pulmonary complications of HAART drugs in HIV patients.
Dhadwal
Ajay K
AK
Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, U.S.A.
Wang
Xinwen
X
Annambhotla
Suman
S
Lin
Peter H
PH
Yao
Qizhi
Q
Chen
Changyi
C
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000704:Analysis of Variance; D000818:Animals; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D001920:Bradykinin; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology*; D004576:Electromyography; D009599:Nitroprusside; D016491:Peripheral Vascular Diseases / Q000139:chemically induced* / Q000188:drug therapy*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000473:pathology; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*
D009599:Nitroprusside; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D019438:Ritonavir; D002211:Capsaicin; D001920:Bradykinin