Rosiglitazone Causes Endothelial Dysfunction in Humans
Journal of Cardiovascular Pharmacology and Therapeutics, 08/10/2012
Perampaladas K et al. – Unexpectedly, therapy with rosiglitazone caused abnormalities in endothelial function in normal volunteers. These findings have important implications with respect to drug development and surveillance.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.
- 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.