Asymmetric dimethylarginine, L-arginine, and endothelial dysfunction in essential hypertension

OBJECTIVES: We investigated the relationship between ADMA plasma levels and endothelium-dependent vasodilation in 36 never-treated essential hypertensives and in 8 normotensive healthy subjects. BACKGROUND: It has been demonstrated that endothelium-dependent vasodilatation is impaired in essential hypertension. The potential contribution of asymmetric dimethylarginine (ADMA) to endothelial dysfunction of hypertensive humans has received poor attention. METHODS: Endothelial function was measured during intra-arterial infusion of acetylcholine (ACh), alone and during co-infusion of L-arginine, and sodium nitroprusside at increasing doses. Concentrations of ADMA and L-arginine in plasma were measured by high-performance liquid chromatography. RESULTS: Hypertensive subjects had significantly higher ADMA and L-arginine plasma concentrations than normotensive healthy controls; ACh-stimulated forearm blood flow (FBF) was significantly reduced in hypertensive subjects in comparison to normotensive control subjects (p < 0.0001). Intra-arterial coinfusion of L-arginine induced a further significant enhancement in ACh-stimulated vasodilation in hypertensive patients. In these, ADMA was strongly and inversely associated with the peak increase in FBF. In a multivariate model, only ADMA and L-arginine were independent correlates, accounting for 33.9% and 8.9% of the variability in the peak FBF response to ACh (p < 0.0001), respectively. CONCLUSIONS: The main finding in this study is that in essential hypertensives the L-arginine and endogenous inhibitor of nitric oxide synthase, ADMA, are inversely related to endothelial function.