The effects of amlodipine and S(-)-amlodipine on vascular endothelial function in patients with hypertension.
Article Details
- CitationCopy to clipboard
He Y, Si D, Yang C, Ni L, Li B, Ding M, Yang P
The effects of amlodipine and S(-)-amlodipine on vascular endothelial function in patients with hypertension.
Am J Hypertens. 2014 Jan;27(1):27-31. doi: 10.1093/ajh/hpt138. Epub 2013 Aug 19.
- PubMed ID
- 23959544 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Levamlodipine Nitric oxide synthase, endothelial Protein Humans UnknownAgonistDetails Levamlodipine Nitric oxide synthase, inducible Protein Humans UnknownAgonistDetails - Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Levamlodipine Nitric oxide synthase, endothelial Protein Humans UnknownInducerDetails Levamlodipine Nitric oxide synthase, inducible Protein Humans UnknownInducerDetails