Dubé Michael P, Gorski Jude Christopher, Shen Changyu
Department of Medicine and the Division of Infectious Diseases, Indiana University School of Medicine, Wishard Memorial Hospital, 1001 W. 10th Street, Suite OPW-430, Indianapolis, IN 46202, USA.
Cardiovasc Toxicol. 2008 Mar;8(1):15-22. doi: 10.1007/s12012-007-9010-y. Epub 2008 Jan 3.
Endothelial dysfunction may contribute to increased cardiovascular events among HIV-1-infected patients receiving antiretroviral therapy. The HIV-1 protease inhibitor indinavir causes both vascular dysfunction and insulin resistance, but the relationship between the two disturbances is not established. Endothelium-dependent vasodilation (EDV), insulin-mediated vasodilation (IMV), and whole body and leg glucose uptake during a euglycemic hyperinsulinemic clamp (40 mU/m(2)/min) were measured before and after four weeks of indinavir in nine healthy men. EDV fell from 270 +/- 67% above basal to 124 +/- 30% (P = 0.04) and IMV from 56 +/- 14% above basal to 8 +/- 8% (P = 0.001) with indinavir. During the clamp, arteriovenous glucose difference and leg glucose uptake were not significantly different after indinavir and whole-body glucose uptake was only modestly reduced (8.0 +/- 0.8 vs. 7.2 +/- 0.8 mg/kg/min, P = 0.04). The change in EDV did not correlate with the change in whole-body glucose uptake after indinavir (r = 0.21, P = 0.6). Despite marked impairment of endothelial function and IMV with indinavir, only modest, inconsistent reductions in measures of insulin-stimulated glucose uptake occurred. This suggests that indinavir's effects on glucose metabolism are not directly related to indinavir-associated endothelial dysfunction. Studies of the vascular effects of newer protease inhibitors are needed.
内皮功能障碍可能导致接受抗逆转录病毒治疗的HIV-1感染患者心血管事件增加。HIV-1蛋白酶抑制剂茚地那韦可导致血管功能障碍和胰岛素抵抗，但这两种紊乱之间的关系尚未明确。在9名健康男性中，在给予茚地那韦治疗4周前后，测量了内皮依赖性血管舒张（EDV）、胰岛素介导的血管舒张（IMV）以及在正常血糖高胰岛素钳夹试验（40 mU/m²/min）期间的全身和腿部葡萄糖摄取。使用茚地那韦后，EDV从基础值以上270±67%降至124±30%（P = 0.04），IMV从基础值以上56±14%降至8±8%（P = 0.001）。在钳夹试验期间，使用茚地那韦后动静脉葡萄糖差值和腿部葡萄糖摄取无显著差异，全身葡萄糖摄取仅略有降低（8.0±0.8对7.2±0.8 mg/kg/min，P = 0.04）。茚地那韦治疗后EDV的变化与全身葡萄糖摄取的变化无相关性（r = 0.21，P = 0.6）。尽管茚地那韦显著损害内皮功能和IMV，但胰岛素刺激的葡萄糖摄取测量值仅出现轻微、不一致的降低。这表明茚地那韦对葡萄糖代谢的影响与茚地那韦相关的内皮功能障碍没有直接关系。需要对新型蛋白酶抑制剂的血管效应进行研究。
