title: Indinavir impairs endothelial function in healthy HIV-negative men.
abstract: BACKGROUND
  Potent antiretroviral treatment has drastically reduced mortality in HIV-infected patients but may accelerate atherosclerotic disease, which could be partially mediated via endothelial dysfunction.
  
  
  METHODS
  In 8 HIV-negative healthy males, leg blood flow responses to intraartery infusions of methacholine chloride (Mch), sodium nitroprusside, and NG-mono-methyl-L-arginine (L-NMMA) were measured before and after 4 weeks of daily oral indinavir. In the same subjects, we also assessed the effect of indinavir on lipids, insulin sensitivity, markers of inflammation, as well as oxidative stress.
  
  
  RESULTS
  After 4 weeks of indinavir, the endothelium-dependent response to methacholine chloride was impaired (195% +/- 38% vs 83% +/- 13%, P < .05), the response to NG-mono-methyl-L-arginine (nitric oxide-dependent tone) was nearly abrogated (-30% +/- 4% vs -1% +/- 11%, P < .05), whereas the endothelium-independent response to sodium nitroprusside remained unchanged. Fasting insulin levels increased from 5.8 +/- 1.2 to 7.0 +/- 1.4 microU/mL (P < .05), and HOMA-IR scores increased from 1.3 +/- 0.3 to 1.6 +/- 0.3 U (P < .05). There were no changes in blood pressure, lipids, markers of inflammation, or oxidative stress.
  
  
  CONCLUSIONS
  Four weeks of the HIV-1 protease inhibitor indinavir, in the absence of HIV-1 infection, causes vascular dysfunction most likely at the level of endothelial nitric oxide production. The vascular dysfunction may be mediated partially by the concomitant induction of insulin resistance but other mechanisms cannot be ruled out.
authors.affiliation: Division of Endocrinology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Sudha S
authors.initials: SS
authors.lastname: Shankar
authors.forename: Michael P
authors.initials: MP
authors.lastname: Dubé
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Gorski
authors.forename: James E
authors.initials: JE
authors.lastname: Klaunig
authors.forename: Helmut O
authors.initials: HO
authors.lastname: Steinberg
mesh_terms: D000328:Adult; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D018023:HIV Seronegativity; D006801:Humans; D019469:Indinavir / Q000494:pharmacology*; D008297:Male; D014664:Vasodilation / Q000187:drug effects
chemical_list: D017320:HIV Protease Inhibitors; D019469:Indinavir