Exogenous L-arginine reduces matrix metalloproteinase-2 and -9 activities and oxidative stress in patients with hypertension

TY - JOUR

T1 - Exogenous L-arginine reduces matrix metalloproteinase-2 and -9 activities and oxidative stress in patients with hypertension

AU - Garcia, Vinicius P

AU - Rocha, Helena N M

AU - Silva, Gustavo M.

AU - Amaral, Tatiana A G

AU - Secher, Niels H.

AU - Nóbrega, Antonio C L

AU - Vianna, Lauro C

AU - Rocha, Natalia G

PY - 2016/7/15

Y1 - 2016/7/15

N2 - Aims 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. Main methods Venous blood samples were obtained from seven patients with hypertension (45 ± 5 yrs., HT group) and eleven normotensive men (37 ± 3 yrs., 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. Key findings 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). Significance 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.

AB - Aims 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. Main methods Venous blood samples were obtained from seven patients with hypertension (45 ± 5 yrs., HT group) and eleven normotensive men (37 ± 3 yrs., 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. Key findings 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). Significance 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.

KW - Hypertension

KW - L-arginine

KW - Matrix metalloproteinases

KW - Nitric oxide

KW - Vascular biomarkers

UR - http://www.scopus.com/inward/record.url?scp=84975471404&partnerID=8YFLogxK

U2 - 10.1016/j.lfs.2016.06.006

DO - 10.1016/j.lfs.2016.06.006

M3 - Journal article

C2 - 27287681

AN - SCOPUS:84975471404

SN - 0024-3205

VL - 157

SP - 125

EP - 130

JO - Life Sciences

JF - Life Sciences

ER -