CLINICAL RESEARCH: HYPERTENSION
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;
revised manuscript received March 22, 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.
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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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