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Diabetes Care Publish Ahead of Print published online ahead of print February 11, 2008
DOI: 10.2337/dc07-2251
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Original Research

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

Valentino Martina, MD1, Andi Masha, MD1, Valentina Ramella Gigliardi, MD1, Loredana Brocato, MD1, Enzo Manzato, MD, PhD3, Arrigo Berchio, MD1, Paola Massarenti, MD1, Fabio Settanni, PhD1, Lara Della Casa2, Stefania Bergamini, PhD2 and Anna Iannone, MD, PhD2

From the 1Department of Internal Medicine, University of Torino, Torino
the 2Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena; and
the 3Department of Medical and Surgical Sciences, University of Padova, Padova (E.M.) Italy

valentino.martina{at}unito.it

ABSTRACT

Objective: Reactive oxygen and nitric oxide (NO) have recently been considered involved in the cardiovascular complications of patients with type 2 diabetes as NO is supposed to loose its physiological beneficial effects, due to the presence of oxygen radicals. For this reason, we tested the effects of L-arginine (ARG) and N-acetylcisteine (NAC) administration to increase the NO bioavailability by reducing the free radical formation.

Research Design and Methods: A double-blind study was performed on 24 male patients with type 2 diabetes and hypertension, divided in 2 groups of 12 patients, which received randomly an oral supplementation of placebo or NAC+ARG, for six months.

Results: The NAC+ARG treatment caused a reduction of the mean arterial blood pressure, both systolic (p<0.05) and diastolic (p<0.05), total-cholesterol (p<0.01), LDL-cholesterol (p<0.005), oxidized-LDL (p<0.05), hs CRP (p<0.05), ICAM (p<0.05), VCAM (p<0.01), nitrotyrosine (p<0.01), fibrinogen (p<0.01), PAI-1 (p<0.05) and intima-media thickness (p<0.02) during endothelial post-ischemic vasodilation. The HDL-cholesterol level increased (p<0.05). No changes in others parameters studied were observed.

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


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