Long-term N-acetylcysteine and L-arginine administration reduces endothelial activation and systolic blood pressure in hypertensive patients with type 2 diabetes.
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.


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.
Martina
Valentino
V
Department of Internal Medicine, University of Torino, Corso Dogliotti 14, I-10121 Torino, Italy. valentino.martina@unito.it
Masha
Andi
A
Gigliardi
Valentina Ramella
VR
Brocato
Loredana
L
Manzato
Enzo
E
Berchio
Arrigo
A
Massarenti
Paola
P
Settanni
Fabio
F
Della Casa
Lara
L
Bergamini
Stefania
S
Iannone
Anna
A
D000111:Acetylcysteine / Q000627:therapeutic use*; D000284:Administration, Oral; D000368:Aged; D001120:Arginine / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D003925:Diabetic Angiopathies / Q000188:drug therapy*; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010919:Placebos; D013599:Systole / Q000187:drug effects
D007004:Hypoglycemic Agents; D010919:Placebos; D001120:Arginine; D000111:Acetylcysteine