Endothelial dysfunction, ADMA and insulin resistance in essential hypertension

Background: Endothelial dysfunction and insulin resistance (IR) are associated with essential hypertension and other cardiovascular risk factors. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, induces endothelial dysfunction in different setting of patients. However, at this moment no data are available about the role of ADMA and IR to induce endothelial dysfunction in an independent way or combined between them. In this study, we investigated, in 63 hypertensives and 21 normotensive healthy subjects, the relationship between ADMA and IR and their possible interaction on endothelial function. Methods: ADMA plasma levels were measured by high-performance liquid chromatography, and IR by homeostasis model assessment (HOMA). Endothelial function was estimated by intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside at increasing doses. Results: Hypertensive patients had significantly higher ADMA, insulin, HOMA and C-reactive protein (CRP) values than normotensive controls (P<0.0001). There were no significant differences in mean L-arginine/ADMA ratio between groups. ACh-stimulated forearm blood flow (FBF) was significantly reduced in hypertensive patients (P<0.0001). In hypertensive group, HOMA was the strongest determinant of FBF, accounting for the 45.5% of its variation. ADMA and gender were the independent determinants of HOMA, accounting for 12.3% and 8.3% of its variation, respectively. Conclusions: The association between ADMA and IR contributes to identify a possible novel mechanism by which ADMA promotes vascular damage, increasing individual cardiovascular risk in hypertensive patients. However, this hypothesis should be tested in a larger study group. (C) 2008 Elsevier Ireland Ltd. All rights reserved.