Rosiglitazone Causes Endothelial Dysfunction in Humans
Objectives: We explored the impact of rosiglitazone on endothelial function in normal volunteers and its interaction with glyceryl trinitrate (GTN)-induced abnormalities in endothelial function. We hypothesized that rosiglitazone would have a neutral effect on endothelial function in normal voluntee...
| Published in: | Journal of Cardiovascular Pharmacology and Therapeutics |
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| Main Authors: | , , |
| Format: | Article in Journal/Newspaper |
| Language: | English |
| Published: |
SAGE Publications
2011
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| Subjects: | |
| Online Access: | http://dx.doi.org/10.1177/1074248411425490 https://journals.sagepub.com/doi/pdf/10.1177/1074248411425490 https://journals.sagepub.com/doi/full-xml/10.1177/1074248411425490 |
| Summary: | Objectives: We explored the impact of rosiglitazone on endothelial function in normal volunteers and its interaction with glyceryl trinitrate (GTN)-induced abnormalities in endothelial function. We hypothesized that rosiglitazone would have a neutral effect on endothelial function in normal volunteers and would favorably modify endothelial dysfunction induced by GTN. Methods: In this double-blind, randomized, placebo-controlled study, 44 participants were randomized to placebo, rosiglitazone (4 mg twice daily), transdermal GTN (0.6 mg/h), or both GTN and rosiglitazone. After 7 days of treatment, participants underwent measures of forearm blood flow during brachial artery infusion of acetylcholine (Ach). Serum glucose concentrations and insulin sensitivity were assessed. Results: Unexpectedly, rosiglitazone-treated participants experienced blunted responses to endothelium-dependent responses to Ach ( P < .05 vs placebo). Sustained GTN administration caused similar abnormalities in endothelial function ( P < .05 vs placebo) and rosiglitazone + GTN ( P < .05 vs placebo; P = ns vs rosiglitazone). Interestingly, co-infusion of the antioxidant vitamin C improved endothelial responses in those randomized to rosiglitazone and GTN alone ( P = not significant [ns] compared with placebo), but it did not improve endothelial function in those treated with rosiglitazone + GTN. Neither rosiglitazone nor GTN treatment modified the measures of glucose metabolism. Conclusions: Unexpectedly, therapy with rosiglitazone caused abnormalities in endothelial function in normal volunteers. These findings have important implications with respect to drug development and surveillance. |
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