TY - JOUR
T1 - Combination therapy with renin-angiotensin system inhibitors and the calcium channel blocker azelnidipine decreases plasma inflammatory markers and urinary oxidative stress markers in patients with diabetic nephropathy
AU - Ogawa, Susumo
AU - Mori, Takefumi
AU - Nako, Kazuhiro
AU - Ito, Sadayoshi
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008/6
Y1 - 2008/6
N2 - A calcium channel blocker (CCB), azelnidipine (AZ), is reported to inhibit oxidative stresses, particularly when administered of the renin-angiotensin system (RAS). The purpose of this study was to investigate whether AZ inhibits oxidative stresses more potently than other CCBs under blockade of RAS and exerts renoprotection in type 2 diabetic nephropathy. Subjects were hypertensive type 2 diabetics with nephropathy, taking RAS inhibitors. The patients were randomly assigned to two groups, an AZ group (n=21, 16 mg/d) and a nifedipine-CR (NF) group (n=17, 40 mg/d). The plasma levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP), adiponectin and tumor necrosis factor-α (TNFα), the urinary excretion of 8-epi-prostaglandin F2α (8-epi-PGF2α) and 8-hydroxy-deoxyguanosine (8-OHdG), and the urinary albumin-to-creatinine ratios (ACR) were determined before and after 16-week treatment. Neither metabolic parameters nor blood pressure levels differed between the two groups not only at baseline but also after the treatment. However, significant decreases in MCP-1, IL-6, hsCRP, TNFα, 8-epi-PGF2α, 8-OHdG and ACR levels, and a significant increase in the plasma adiponectin level were detected in the AZ group, but not in the NF group. The % change in the urinary oxidative stress markers correlated with that in ACR. Our results indicate that, in hypertensive patients with diabetic nephropathy, a combination therapy of RAS inhibitors and AZ is an effective therapeutic modality for decreasing not only blood pressure but also inflammations and oxidative stresses.
AB - A calcium channel blocker (CCB), azelnidipine (AZ), is reported to inhibit oxidative stresses, particularly when administered of the renin-angiotensin system (RAS). The purpose of this study was to investigate whether AZ inhibits oxidative stresses more potently than other CCBs under blockade of RAS and exerts renoprotection in type 2 diabetic nephropathy. Subjects were hypertensive type 2 diabetics with nephropathy, taking RAS inhibitors. The patients were randomly assigned to two groups, an AZ group (n=21, 16 mg/d) and a nifedipine-CR (NF) group (n=17, 40 mg/d). The plasma levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP), adiponectin and tumor necrosis factor-α (TNFα), the urinary excretion of 8-epi-prostaglandin F2α (8-epi-PGF2α) and 8-hydroxy-deoxyguanosine (8-OHdG), and the urinary albumin-to-creatinine ratios (ACR) were determined before and after 16-week treatment. Neither metabolic parameters nor blood pressure levels differed between the two groups not only at baseline but also after the treatment. However, significant decreases in MCP-1, IL-6, hsCRP, TNFα, 8-epi-PGF2α, 8-OHdG and ACR levels, and a significant increase in the plasma adiponectin level were detected in the AZ group, but not in the NF group. The % change in the urinary oxidative stress markers correlated with that in ACR. Our results indicate that, in hypertensive patients with diabetic nephropathy, a combination therapy of RAS inhibitors and AZ is an effective therapeutic modality for decreasing not only blood pressure but also inflammations and oxidative stresses.
KW - Albuminuria
KW - Azelnidipine
KW - Diabetic nephropathy
KW - Inflammation
KW - Oxidative stress
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U2 - 10.1291/hypres.31.1147
DO - 10.1291/hypres.31.1147
M3 - Article
C2 - 18716362
AN - SCOPUS:48349097293
VL - 31
SP - 1147
EP - 1155
JO - Hypertension Research
JF - Hypertension Research
SN - 0916-9636
IS - 6
ER -