title: The effects of amlodipine and S(-)-amlodipine on vascular endothelial function in patients with hypertension.
abstract: BACKGROUND
  Amlodipine has been shown to improve vascular endothelial function in hypertensive patients, but whether S(-)-amlodipine has a similar effect remains controversial. This study compared the effects of amlodipine and S(-)-amlodipine on vascular endothelial function in hypertensive patients and investigated relevant mechanisms of action in cell culture.
  
  
  METHODS
  Twenty-four patients with essential hypertension received amlodipine and S(-)-amlodipine for 6 weeks in a randomized, crossover study. Associated flow-mediated dilation (FMD), nitric oxide (NO), and endothelial nitric oxide synthase (eNOS) levels were determined. NO levels were measured after exposure of human umbilical vein endothelial cells (HUVECs) to amlodipine, S(-)-amlodipine, the eNOS inhibitor N w-nitro-L-arginine (L-NA), and the Protein Kinase C (PKC) inhibitor Ro 31-8220. Phosphorylation levels of Ser(1177) and Thr(495) in eNOS were determined after exposure to amlodipine, S(-)-amlodipine, and Ro 31-8220.
  
  
  RESULTS
  FMD, NO, and eNOS levels significantly improved after treatment with amlodipine and S(-)-amlodipine. The levels were all higher with amlodipine, although the between-treatment difference was not statistically significant. Amlodipine and S(-)-amlodipine significantly increased NO levels in cultured HUVECs, but increases in NO levels were more marked with amlodipine. Western blot assay showed that both amlodipine and Ro31-8220 induced Ser(1177) phosphorylation and weakened Thr(495) phosphorylation in eNOS. S(-)-amlodipine had no similar effects. Amlodipine, but not S(-)-amlodipine, decreased the PKC phosphorylation in a time-dependent manner.
  
  
  CONCLUSIONS
  Amlodipine and S(-)-amlodipine can both improve endothelial function in hypertensive patients. Amlodipine has greater potential for vascular endothelial protection than S(-)-amlodipine. It affects eNOS phosphorylation at Ser(1177) and Thr(495) by the PKC pathway, further enhancing eNOS activation.
authors: Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun, China.
authors: Yuquan
authors: Y
authors: He
authors: Daoyuan
authors: D
authors: Si
authors: Chunyan
authors: C
authors: Yang
authors: Lujia
authors: L
authors: Ni
authors: Bing
authors: B
authors: Li
authors: Mei
authors: M
authors: Ding
authors: Ping
authors: P
authors: Yang
mesh_terms: D017311:Amlodipine / Q000737:chemistry / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000737:chemistry / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000627:therapeutic use*; D002478:Cells, Cultured; D002681:China; D018592:Cross-Over Studies; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013997:Time Factors; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D047428:Protein Kinase Inhibitors; D014665:Vasodilator Agents; D017311:Amlodipine; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D011493:Protein Kinase C
keywords: Doppler ultrasonography; S(-)-amlodipine.; amlodipine; blood pressure; endothelial function; hypertension; phosphorylation