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

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
  • 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)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: