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CLINICAL RESEARCH

Asymmetric Dimethylarginine, L-Arginine, and Endothelial Dysfunction in Essential Hypertension

Francesco Perticone, MD^_*,_*, Angela Sciacqua, MD^_*, Raffaele Maio, MD^_*, Maria Perticone, MD^_*, Renke Maas, MD, Rainer H. Boger, MD, Giuseppe Tripepi, Stat Tech, Giorgio Sesti, MD^_* and Carmine Zoccali, MD

^_* Internal Medicine and Cardiovascular Diseases Unit, Department of Medicina Sperimentale e Clinica "G. Salvatore," University Magna Graecia of Catanzaro, Catanzaro, Italy
Clinical Pharmacology Unit, Department of Pharmacology, University Hospital Hamburg-Eppendorf, Hamburg-Eppendorf, Germany
CNR-IBIM, National Research Council-Institute of Biomedicine, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Reggio Calabria, Italy.

Manuscript received January 26, 2005; accepted April 13, 2005.

^_* Reprint requests and correspondence: Dr. Francesco Perticone, Department of Medicina Sperimentale e Clinica, Policlinico Mater Domini, Via Tommaso Campanella, 88100 Catanzaro, Italy (Email: perticone{at}unicz.it).

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.

Abbreviations and Acronyms   ACh = acetylcholine   ADMA = asymmetric dimethylarginine   BMI = body mass index   BP = blood pressure   e-NOS = endothelial nitric oxide synthase   FBF = forearm blood flow   HR = heart rate   NO = nitric oxide   SNP = sodium nitroprusside   VR = vascular resistance

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