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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.
AuthorsMakoto Sumi, Masataka Sata, Ayako Hashimoto, Takashi Imaizumi, Katsuhiko Yanaga, Takao Ohki, Toyoki Mori, Ryozo Nagai
JournalBiomedicine & pharmacotherapy = Biomédecine & pharmacothérapie (Biomed Pharmacother) Vol. 61 Issue 4 Pg. 209-15 (May 2007) ISSN: 0753-3322 [Print] France
PMID17223008 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Aniline Compounds
  • OPC 28326
  • Piperidines
  • Vasodilator Agents
  • Nitric Oxide Synthase Type III
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)

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