Indinavir impairs endothelial function in healthy HIV-negative men

Sudha S. Shankar, Michael P. Dubé, J. Christopher Gorski, James E. Klaunig, Helmut Steinberg

Research output: Contribution to journalArticle

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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 μU/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.

Original languageEnglish (US)
Pages (from-to)933.e1-933.e7
JournalAmerican Heart Journal
Volume150
Issue number5
DOIs
StatePublished - Jan 1 2005
Externally publishedYes

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Indinavir
HIV
Methacholine Chloride
Nitroprusside
Endothelium
Blood Vessels
Arginine
Insulin Resistance
Nitric Oxide
Oxidative Stress
HIV Protease Inhibitors
Inflammation
Lipids
HIV Infections
HIV-1
Fasting
Leg
Insulin
Blood Pressure
Mortality

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Indinavir impairs endothelial function in healthy HIV-negative men. / Shankar, Sudha S.; Dubé, Michael P.; Gorski, J. Christopher; Klaunig, James E.; Steinberg, Helmut.

In: American Heart Journal, Vol. 150, No. 5, 01.01.2005, p. 933.e1-933.e7.

Research output: Contribution to journalArticle

Shankar, SS, Dubé, MP, Gorski, JC, Klaunig, JE & Steinberg, H 2005, 'Indinavir impairs endothelial function in healthy HIV-negative men', American Heart Journal, vol. 150, no. 5, pp. 933.e1-933.e7. https://doi.org/10.1016/j.ahj.2005.06.005
Shankar, Sudha S. ; Dubé, Michael P. ; Gorski, J. Christopher ; Klaunig, James E. ; Steinberg, Helmut. / Indinavir impairs endothelial function in healthy HIV-negative men. In: American Heart Journal. 2005 ; Vol. 150, No. 5. pp. 933.e1-933.e7.
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AU - Steinberg, Helmut

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AB - 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 μU/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.

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