Azelnidipine, a dihydropyridine-based calcium antagonist, inhibits angiotensin II-induced oxidative stress generation and downregulation of pigment epithelium-derived factor mRNA levels in microvascular endothelial cells

T. Matsui, S. Yamagishi, K. Nakamura, S. Kikuchi, Hiroyoshi Inoue

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

We have previously shown that azelnidipine, a long-acting dihydropyridine-based calcium antagonist (DHP), inhibited tumor necrosis factor-α-induced endothelial cell (EC) activation through its antioxidative properties. However, whether azelnidipine could also block the angiotensin II (Ang II)-signaling in ECs remains to be elucidated. Since Ang II-type 1 receptor interaction could contribute to exacerbation of diabetic retinopathy by downregulating pigment epithelium-derived factor (PEDF) gene expression in ECs, we examined here whether azelnidipine inhibited the Ang II-induced reactive oxygen species (ROS) generation and subsequent PEDF gene suppression in microvascular ECs. Azelnidipine, but not nitrendipine, the other popular DHP, completely inhibited the Ang II-induced ROS generation in ECs. Furthermore, azelnidipine, but not nitrendipine, was found to partially restore decreased PEDF mRNA levels in Ang II-exposed ECs. The present study suggests that azelnidipine could inhibit the Ang II-induced decrease in PEDF mRNA levels in ECs through its antioxidative properties. Upregulation of PEDF by azelnidipine may become a therapeutic target for the treatment of diabetic retinopathy associated with hypertension.

Original languageEnglish
Pages (from-to)215-219
Number of pages5
JournalDrugs under Experimental and Clinical Research
Volume31
Issue number5-6
Publication statusPublished - 2005
Externally publishedYes

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Angiotensin II
Oxidative Stress
Down-Regulation
Endothelial Cells
Calcium
Messenger RNA
Nitrendipine
Diabetic Retinopathy
Reactive Oxygen Species
Angiotensin Type 1 Receptor
1,4-dihydropyridine
azelnidipine
pigment epithelium-derived factor
Up-Regulation
Tumor Necrosis Factor-alpha
Hypertension
Gene Expression
Genes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology (medical)
  • Pharmacology
  • Drug Discovery

Cite this

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abstract = "We have previously shown that azelnidipine, a long-acting dihydropyridine-based calcium antagonist (DHP), inhibited tumor necrosis factor-α-induced endothelial cell (EC) activation through its antioxidative properties. However, whether azelnidipine could also block the angiotensin II (Ang II)-signaling in ECs remains to be elucidated. Since Ang II-type 1 receptor interaction could contribute to exacerbation of diabetic retinopathy by downregulating pigment epithelium-derived factor (PEDF) gene expression in ECs, we examined here whether azelnidipine inhibited the Ang II-induced reactive oxygen species (ROS) generation and subsequent PEDF gene suppression in microvascular ECs. Azelnidipine, but not nitrendipine, the other popular DHP, completely inhibited the Ang II-induced ROS generation in ECs. Furthermore, azelnidipine, but not nitrendipine, was found to partially restore decreased PEDF mRNA levels in Ang II-exposed ECs. The present study suggests that azelnidipine could inhibit the Ang II-induced decrease in PEDF mRNA levels in ECs through its antioxidative properties. Upregulation of PEDF by azelnidipine may become a therapeutic target for the treatment of diabetic retinopathy associated with hypertension.",
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AU - Matsui, T.

AU - Yamagishi, S.

AU - Nakamura, K.

AU - Kikuchi, S.

AU - Inoue, Hiroyoshi

PY - 2005

Y1 - 2005

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