title: 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.
abstract: 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-alpha (TNF(alpha)), the urinary excretion of 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)) 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(alpha), 8-epi-PGF(2alpha), 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.
authors: Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Hospital, Aoba-ku, Sendai, Japan. ogawa-s@mail.tains.tohoku.ac.jp
authors: Susumu
authors: S
authors: Ogawa
authors: Takefumi
authors: T
authors: Mori
authors: Kazuhiro
authors: K
authors: Nako
authors: Sadayoshi
authors: S
authors: Ito
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D001383:Azetidinecarboxylic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002097:C-Reactive Protein / Q000032:analysis; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D003404:Creatinine / Q000652:urine; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism; D004095:Dihydropyridines / Q000008:administration & dosage*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D015850:Interleukin-6; C075750:8-epi-prostaglandin F2alpha; D001383:Azetidinecarboxylic Acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002097:C-Reactive Protein; D003404:Creatinine; D015237:Dinoprost; D003849:Deoxyguanosine; C061679:azelnidipine