Calcium channel blocker, azelnidipine, reduces lipid hydroperoxides in patients with type 2 diabetes independent of blood pressure

Endocr J. 2007 Dec;54(5):805-11. doi: 10.1507/endocrj.k07-063. Epub 2007 Sep 25.

Abstract

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.

Publication types

  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Amlodipine / therapeutic use
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use
  • Ascorbic Acid / administration & dosage
  • 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, Type 2 / complications
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Dihydropyridines / pharmacology*
  • Dihydropyridines / therapeutic use*
  • Erythrocytes / chemistry
  • Erythrocytes / drug effects
  • Female
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Lipid Peroxides / analysis
  • Lipid Peroxides / metabolism*
  • Male
  • Middle Aged
  • Organophosphorus Compounds / chemistry
  • Organophosphorus Compounds / pharmacology
  • Pyrenes / chemistry
  • Pyrenes / pharmacology
  • Vitamin E / administration & dosage

Substances

  • Antihypertensive Agents
  • Calcium Channel Blockers
  • Dihydropyridines
  • Lipid Peroxides
  • Organophosphorus Compounds
  • Pyrenes
  • diphenyl-1-pyrenylphosphine
  • Vitamin E
  • Amlodipine
  • Azetidinecarboxylic Acid
  • Ascorbic Acid
  • azelnidipine