OPC-28326, a selective femoral arterial vasodilator, augments ischemia induced angiogenesis.

Abstract

OPC-28326, 4-(N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionyl-aminobenzoyl) piperidine hydrochloride monohydrate, is a newly developed selective peripheral vasodilator and increases blood flow to lower extremities with alpha2-adrenergic antagonist property. Here, we investigated the effect of OPC-28326 on ischemia-induced angiogenesis. OPC-28326 enhanced tube formation by human aortic endothelial cells (HAECs). Moreover, OPC-28326 enhanced the number of microvessels sprouting from aortic rings embedded in collagen gel. OPC-28326 markedly induced phosphorylation of endothelial nitric oxide synthase (eNOS) in HAECs via phosphatidylinositol-3 kinase PI3K/Akt (PI3K/Akt) pathway. Next, the angiogenic effect of OPC-28326 was evaluated in a mouse hindlimb ischemia model. Blood flow recovery to the ischemic leg was significantly enhanced by OPC-28326. Furthermore, anti-CD31 immunostaining revealed that OPC-28326 increased capillary density in the ischemic muscle. However, OPC-28326 failed to promote blood flow recovery in ischemic hindlimb in eNOS-deficient mice. These results suggest that OPC-28326 promotes angiogenesis, which was associated with activation of eNOS via PI3K/Akt pathway. OPC-28326 might be promising to treat patients with ischemic vascular diseases.

• Authors: Makoto Sumi, Masataka Sata, Ayako Hashimoto, Takashi Imaizumi, Katsuhiko Yanaga, Takao Ohki, Toyoki Mori, Ryozo Nagai
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 61 Issue 4 Pg. 209-15 (May 2007) ISSN: 0753-3322 [Print] France
• PMID: 17223008 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aniline Compounds
• Piperidines
• Vasodilator Agents
• Nitric Oxide Synthase Type III
• OPC 28326

Topics

• Aniline Compounds (pharmacology)
• Animals
• Aorta (cytology, drug effects, physiology)
• Blotting, Western
• Cells, Cultured
• Dose-Response Relationship, Drug
• Endothelial Cells (drug effects, metabolism)
• Endothelium, Vascular (cytology)
• Hindlimb (blood supply)
• Humans
• In Vitro Techniques
• Ischemia (physiopathology)
• Laser-Doppler Flowmetry
• Mice
• Mice, Inbred C3H
• Mice, Inbred C57BL
• Neovascularization, Physiologic (drug effects)
• Nitric Oxide Synthase Type III (genetics, metabolism)
• Phosphorylation
• Piperidines (pharmacology)
• Rats
• Regional Blood Flow
• Vasodilator Agents (pharmacology)