Calcium Channel Blocker, Azelnidipine, Reduces Lipid Hydroperoxides in Patients with Type 2 Diabetes Independent of Blood Pressure

• Published in: Endocrine Journal Vol. 54; no. 5; pp. 805 - 811
• Main Authors: KANAZAWA, Akio, HIROSE, Takahisa, SAKAI, Ken, UCHINO, Hiroshi, KAWAMORI, Ryuzo, SHIMIZU, Tomoaki, OHMURA, Chie, FUJITANI, Yoshio, WATADA, Hirotaka
• Format: Journal Article
• Language: English
• Published: Japan The Japan Endocrine Society 2007
• Subjects: Adult; Aged; Amlodipine - therapeutic use; Antihypertensive Agents - pharmacology; Antihypertensive Agents - therapeutic use; Ascorbic Acid - administration & dosage; Azelnidipine; Azetidinecarboxylic Acid - analogs & derivatives; Azetidinecarboxylic Acid - pharmacology; Azetidinecarboxylic Acid - therapeutic use; Blood Pressure - drug effects; Calcium Channel Blockers - pharmacology; Calcium Channel Blockers - therapeutic use; Diabetes mellitus; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - physiopathology; Dihydropyridines - pharmacology; Dihydropyridines - therapeutic use; Diphenyl-1-pyrenylphosphine (DPPP); Erythrocytes - chemistry; Erythrocytes - drug effects; Female; Humans; Hypertension; Hypertension - complications; Hypertension - drug therapy; Lipid hydroperoxides; Lipid Peroxides - analysis; Lipid Peroxides - metabolism; Male; Middle Aged; Organophosphorus Compounds - chemistry; Organophosphorus Compounds - pharmacology; Oxidative stress; Pyrenes - chemistry; Pyrenes - pharmacology; Vitamin E - administration & dosage
• ISSN: 0918-8959; 1348-4540; 1348-4540
• DOI: 10.1507/endocrj.K07-063

Anti-hypertensive agents with antioxidative effects are potentially useful for diabetic patients with hypertension to prevent the onset and progression of their complication. While dihydropyridine-type calcium antagonists are among the frequently used anti-hypertensive drugs, azelnidipine, a novel calcium antagonist, has been reported to have a unique anti-oxidative effect in vitro and in animals. In this study, we measured lipid hydroperoxides in human sample using diphenyl-1-pyrenylphosphine for the first time, and used the value of lipid hydroperoxides as an index of oxidative stress. Then, we compared the antioxidative properties of azelnidipine and amlodipine, a frequently used calcium antagonist in hypertensive diabetic patients. Administration of vitamin C and E for 8 weeks significantly reduced lipid hydroperoxides in erythrocyte membrane in normal subjects. In hypertensive diabetic patients, azelnidipine treatment for 12 weeks induced a more significant fall in erythrocyte lipid hydroperoxide level than amlodipine, though blood pressure during each treatment was comparable. Our data confirm the usefulness of lipid hydroperoxides in erythrocyte membrane as a marker of oxidative stress in vivo, and indicate that azelnidipine has a unique antioxidative property in human.