Calcium channel blocker, azelnidipine, reduces lipid hydroperoxides in patients with type 2 diabetes independent of blood pressure.
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.
Ohmura
Chie
C
Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo, Japan.
Watada
Hirotaka
H
Shimizu
Tomoaki
T
Sakai
Ken
K
Uchino
Hiroshi
H
Fujitani
Yoshio
Y
Kanazawa
Akio
A
Hirose
Takahisa
T
Kawamori
Ryuzo
R
D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000008:administration & dosage; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology*; D004095:Dihydropyridines / Q000494:pharmacology* / Q000627:therapeutic use*; D004912:Erythrocytes / Q000737:chemistry / Q000187:drug effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008054:Lipid Peroxides / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000494:pharmacology; D011721:Pyrenes / Q000737:chemistry / Q000494:pharmacology; D014810:Vitamin E / Q000008:administration & dosage
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D008054:Lipid Peroxides; D009943:Organophosphorus Compounds; D011721:Pyrenes; C066322:diphenyl-1-pyrenylphosphine; D014810:Vitamin E; D017311:Amlodipine; D001383:Azetidinecarboxylic Acid; D001205:Ascorbic Acid; C061679:azelnidipine