Exogenous l-arginine reduces matrix metalloproteinase-2 and -9 activities and oxidative stress in patients with hypertension.
OBJECTIVE
Increased matrix metalloproteinases activity and reduced nitric oxide (NO) bioavailability contributes to development of hypertension and this may be associated with a defective l-arginine-NO pathway. Exogenous l-arginine improves endothelial function to prevent the onset of cardiovascular disease, but the mechanism by which this is accomplished remains unclear. We determined the effects of exogenous l-arginine infusion on vascular biomarkers in patients with hypertension.


METHODS
Venous blood samples were obtained from seven patients with hypertension (45±5yrs., HT group) and eleven normotensive men (37±3yrs., CT group) before and during a 30-min intravenous l-arginine or saline infusion. Nitrite concentration was evaluated by ozone-chemiluminescence method; metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) activities were detected by zymography; tissue inhibitor of metalloproteinases-1 (TIMP-1) and 8-isoprostane concentrations were measured by enzyme-linked immunosorbent assay (ELISA); and thiobarbituric acid reactive substances (TBARS) were determined by colorimetric assay.


RESULTS
At baseline, nitrite, TIMP-1, and MMP-2 activity were similar between the groups (P>0.05), but MMP-9, TBARS and 8-isoprostane were higher in HT group (P≤0.03). During l-arginine infusion, nitrite increased only in control group (P=0.01), while MMP-2, MMP-9 activities, MMP-9/TIMP-1 ratio and 8-isoprostane decreased in HT group (P≤0.02). There were no significant changes in vascular biomarkers between groups during the saline infusion (P>0.05).


CONCLUSIONS
Exogenous l-arginine diminished metalloproteinase-2 and -9 activities and MMP-9/TIMP-1 ratio along with restoring the oxidative stress balance in patients with hypertension.
Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niterói, Brazil.
Vinicius P
VP
Garcia
Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niterói, Brazil.
Helena N M
HNM
Rocha
Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niterói, Brazil.
Gustavo M
GM
Silva
Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niterói, Brazil.
Tatiana A G
TAG
Amaral
Department of Anaesthesiology, The Copenhagen Muscle Research Center, Rigshospitalet, University of Copenhagen, Denmark.
Niels H
NH
Secher
Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niterói, Brazil.
Antonio C L
ACL
Nóbrega
Faculty of Physical Education, University of Brasília, Brasília, Brazil.
Lauro C
LC
Vianna
Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niterói, Brazil. Electronic address: nataliagalito@id.uff.br.
Natália G
NG
Rocha
D000328:Adult; D001120:Arginine / Q000494:pharmacology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*
D001120:Arginine; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
Hypertension; Matrix metalloproteinases; Nitric oxide; Vascular biomarkers; l-arginine