title: Effects of calcium channel blockers on glucose tolerance, inflammatory state, and circulating progenitor cells in non-diabetic patients with essential hypertension: a comparative study between azelnidipine and amlodipine on glucose tolerance and endothelial function--a crossover trial (AGENT).
abstract: BACKGROUND
  Hypertension is associated with impaired glucose tolerance and insulin resistance. Medical treatment that interferes with various steps in the renin-angiotensin system improves glucose tolerance and insulin resistance. However, it remains unclear if long-acting calcium channel blockers (CCBs) such as azelnidipine and amlodipine affect glucose tolerance and insulin resistance in clinical practice.
  
  
  METHODS
  Seventeen non-diabetic patients with essential hypertension who had controlled blood pressure levels using amlodipine (5 mg/day) were enrolled in this study. After randomization, either azelnidipine (16 mg/day) or amlodipine (5 mg/day) was administered in a crossover design for 12-weeks. At baseline and the end of each CCB therapy, samples of blood and urine were collected and 75 g oral glucose tolerance test (OGTT) was performed. In addition, hematopoietic progenitor cells (HPCs) were measured at each point by flow cytometry and endothelial functions were measured by fingertip pulse amplitude tonometry using EndoPAT.
  
  
  RESULTS
  Although blood pressure levels were identical after each CCB treatment, the heart rate significantly decreased after azelnidipine administration than that after amlodipine administration (P < 0.005). Compared with amlodipine administration, azelnidipine significantly decreased levels of glucose and insulin 120 min after the 75 g OGTT (both P < 0.05). Serum levels of high-sensitivity C-reactive protein (P = 0.067) and interleukin-6 (P = 0.035) were decreased. Although endothelial functions were not different between the two medication groups, the number of circulating HPCs was significantly increased after azelnidipine administration (P = 0.016).
  
  
  CONCLUSIONS
  These results suggest that azelnidipine treatment may have beneficial effects on glucose tolerance, insulin sensitivity, the inflammatory state, and number of circulating progenitor cells in non-diabetic patients with essential hypertension.
authors: Department of Cardiovascular Medicine, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors: Kosuke
authors: K
authors: Fukao
authors: Kazunori
authors: K
authors: Shimada
authors: Makoto
authors: M
authors: Hiki
authors: Takashi
authors: T
authors: Kiyanagi
authors: Kuniaki
authors: K
authors: Hirose
authors: Atsumi
authors: A
authors: Kume
authors: Hiromichi
authors: H
authors: Ohsaka
authors: Rie
authors: R
authors: Matsumori
authors: Takeshi
authors: T
authors: Kurata
authors: Tetsuro
authors: T
authors: Miyazaki
authors: Hiroyuki
authors: H
authors: Daida
mesh_terms: D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000494:pharmacology / Q000627:therapeutic use*; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004095:Dihydropyridines / Q000494:pharmacology / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
chemical_list: D001786:Blood Glucose; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D017311:Amlodipine; D001383:Azetidinecarboxylic Acid; C061679:azelnidipine