Cardiovascular Toxicology

, Volume 8, Issue 1, pp 15–22

Severe Impairment of Endothelial Function with the HIV-1 Protease Inhibitor Indinavir is not Mediated by Insulin Resistance in Healthy Subjects


    • Department of Medicine and the Division of Infectious DiseasesIndiana University School of Medicine, Wishard Memorial Hospital
  • Jude Christopher Gorski
    • Division of Clinical PharmacologyIndiana University School of Medicine
    • Mylan Pharmaceuticals, Inc.
  • Changyu Shen
    • Division of BiostatisticsIndiana University School of Medicine

DOI: 10.1007/s12012-007-9010-y

Cite this article as:
Dubé, M.P., Gorski, J.C. & Shen, C. Cardiovasc Toxicol (2008) 8: 15. doi:10.1007/s12012-007-9010-y


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/m2/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.


Endothelial dysfunctionInsulin sensitivityIndinavirHIV-1 protease inhibitors



Endothelium-dependent vasodilation


Insulin-mediated vasodilation


Nitric oxide




Arterio-venous glucose difference

Copyright information

© Humana Press Inc. 2007