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

• Published in: Hypertension research Vol. 31; no. 6; pp. 1147 - 1155
• Main Authors: Ogawa, Susumu, Mori, Takefumi, Nako, Kazuhiro, Ito, Sadayoshi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2008
• Subjects: Adult; Aged; albuminuria; Angiotensin II Type 1 Receptor Blockers - administration & dosage; Angiotensin-Converting Enzyme Inhibitors - administration & dosage; azelnidipine; Azetidinecarboxylic Acid - administration & dosage; Azetidinecarboxylic Acid - analogs & derivatives; C-Reactive Protein - analysis; Calcium Channel Blockers - administration & dosage; Creatinine - urine; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - urine; Diabetic Nephropathies - drug therapy; Diabetic Nephropathies - metabolism; diabetic nephropathy; Dihydropyridines - administration & dosage; Dinoprost - analogs & derivatives; Dinoprost - urine; Drug Therapy, Combination; Female; Geriatrics/Gerontology; Health Promotion and Disease Prevention; Humans; inflammation; Interleukin-6 - blood; Internal Medicine; Male; Medicine; Medicine & Public Health; Middle Aged; Obstetrics/Perinatology/Midwifery; original-article; Oxidative Stress; Public Health; albuminuria; azelnidipine; inflammation; diabetic nephropathy; oxidative stress
• ISSN: 0916-9636; 1348-4214
• DOI: 10.1291/hypres.31.1147

A calcium channel blocker (CCB), azelnidipine (AZ), is reported to inhibit oxidative stresses, particularly when administered under blockade 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 (TNF α ), the urinary excretion of 8-epi-prostaglandin F 2α (8-epi-PGF 2α ) and 8-hydroxydeoxyguanosine (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, TNF α , 8-epi-PGF 2α , 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.