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. MATERIAL/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.
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机译：背景：包括 HIV 蛋白酶抑制剂利托那韦在内的高效抗逆转录病毒疗法 （HAART） 可能与临床并发症有关，包括加速动脉粥样硬化和肺动脉高压。本研究的目的是确定辣椒素（辣椒的主要成分）具有抗氧化特性，是否能有效抑制利托那韦诱导的猪肺动脉氧化损伤。材料/方法： 用利托那韦 （15 μM）、辣椒素 （50 μM） 或两者处理新鲜猪肺动脉环 24 小时，然后进行肌图分析以响应血管活性药物，包括血栓素 A2 类似物 U-46619、缓激肽和硝普钠 （SNP）。结果：与对照环相比，利托那韦治疗的猪肺动脉环响应 U-46619 （3x10（-8） M，收缩减少 15%。与未治疗的对照血管相比，利托那韦治疗的环对缓激肽 （10（-6） M） 的内皮依赖性血管松弛显着降低 32%（P<0.05，n=5，Student t 检验）。然而，利托那韦治疗并未改变响应 SNP 的内皮非依赖性血管舒张 （10（-6） M）。与未处理的对照血管相比，辣椒素处理的血管环对 U-46619、缓激肽和 SNP 的反应没有显示出任何显着变化。更重要的是，与单独使用利托那韦治疗相比，辣椒素与利托那韦共培养可显著阻断利托那韦诱导的猪肺动脉环内皮依赖性血管舒张和收缩抑制（P<0.05，n=5，学生t检验）。结论：辣椒素有效抑制HIV蛋白酶抑制剂利托那韦对猪肺动脉血管舒缩功能的不利影响。这些发现可能表明，辣椒素可能具有临床应用，以预防HAART药物在HIV患者中的血管和肺部并发症。
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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.;
