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.
|Number of pages||5|
|Journal||Drugs under Experimental and Clinical Research|
|Publication status||Published - 2005 Dec 1|
ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery
- Pharmacology (medical)