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Long-Term N-Acetylcysteine and L-Arginine Administration Reduces Endothelial Activation and Systolic Blood Pressure in Hypertensive Patients With Type 2 Diabetes

¹ Department of Internal Medicine, University of Torino, Torino, Italy
² Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy
³ Department of Medical and Surgical Sciences, University of Padova, Padova, Italy

Corresponding author: Valentino Martina, MD, Department of Internal Medicine, University of Torino, Corso Dogliotti 14, I-10121 Torino, Italy. E-mail: valentino.martina{at}unito.it

OBJECTIVE—Reactive oxygen and nitric oxide (NO) have recently been considered to be involved in the cardiovascular complications of patients with type 2 diabetes, as NO is thought to lose its beneficial physiological effects in the presence of oxygen radicals. For this reason, we tested the effects of L-arginine (ARG) and N-acetylcysteine (NAC) administration in increasing NO bioavailability by reducing free radical formation.

RESEARCH DESIGN AND METHODS—A double-blind study was performed on 24 male patients with type 2 diabetes and hypertension divided into two groups of 12 patients that randomly received either an oral supplementation of placebo or NAC + ARG for 6 months.

RESULTS—The NAC + ARG treatment caused a reduction of both systolic (P < 0.05) and diastolic (P < 0.05) mean arterial blood pressure, total cholesterol (P < 0.01), LDL cholesterol (P < 0.005), oxidized LDL (P < 0.05), high-sensitive C-reactive protein (P < 0.05), intracellular adhesion molecule (P < 0.05), vascular cell adhesion molecule (P < 0.01), nitrotyrosine (P < 0.01), fibrinogen (P < 0.01), and plasminogen activator inhibitor-1 (P < 0.05), and an improvement of the intima-media thickness during endothelial postischemic vasodilation (P < 0.02). HDL cholesterol increased (P < 0.05). No changes in other parameters studied were observed.

CONCLUSIONS—NAC + ARG administration seems to be a potential well-tolerated antiatherogenic therapy because it improves endothelial function in hypertensive patients with type 2 diabetes by improving NO bioavailability via reduction of oxidative stress and increase of NO production. Our study's results give prominence to its potential use in primary and secondary cardiovascular prevention in these patients.

Abbreviations: ABP, arterial blood pressure • ABPM, ambulatory blood pressure monitoring • ADMA, asymmetrical dimethyl-arginine • ARG, L-arginine • hs-CRP, high-sensitive C-reactive protein • sGC, soluble guanylyl cyclase • cGMP, intracellular guanosine 3',5'-cyclic monophosphate • GSH, glutathione • GSSG, oxidized glutathione • HPLC, high-performance liquid chromatography • ICAM, intercellular adhesion molecule • IL-6, interleukin-6 • IMT, intima-media thickness • ox-LDL, oxidized LDL • NAC, N-acetylcysteine • cNOS, constitutive NO synthase • PAI-1, plasminogen activator inhibitor-1 • ROS, reactive oxygen species • SDMA, symmetrical dimethyl-arginine • TNF-, tumor necrosis factor- • VCAM, vascular cell adhesion molecule

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