Angiopeptin enhances acetylcholine-induced relaxation and inhibits intimal hyperplasia after vascular injury.
The effects of the somatostatin analogue, angiopeptin (BIM-23014), on neoendothelial function, as evidenced by formation of prostaglandin (PG) I2 and by acetylcholine-induced relaxation (formation of endothelial-derived relaxing factor), were investigated in the rabbit aorta. A balloon catheter injury of the thoracic and abdominal aorta was induced in New Zealand White rabbits. Animals treated with angiopeptin for 2 or 4 wk were compared with untreated rabbits at 2 or 4 wk after the induction of injury, as well as to sham-operated controls. When the rabbits were killed, vascular rings were assessed for arachidonic acid-stimulated PGI2 formation, acetylcholine-induced relaxation, and the degree of intimal hyperplasia. Vascular rings from animals treated with angiopeptin exhibited enhanced acetylcholine-induced relaxation; however, angiopeptin treatment had no effect on arachidonic acid-stimulated PGI2 formation. Intimal hyperplasia in treated animals was reduced by 36%. Treatment with another somatostatin analogue, BIM-23030, did not enhance relaxation or inhibit intimal hyperplasia. These data suggest that treatment with angiopeptin may inhibit intimal hyperplasia in part by its beneficial effect on neoendothelial function.
Light
J T
JT
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Bellan
J A
JA
Chen
I L
IL
Longenecker
L L
LL
Murphy
W A
WA
Coy
D H
DH
Kadowitz
P J
PJ
McNamara
D B
DB
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000293:injuries* / Q000378:metabolism; D016718:Arachidonic Acid / Q000494:pharmacology; D002404:Catheterization; D004357:Drug Synergism; D015777:Eicosanoids / Q000096:biosynthesis; D008297:Male; D008855:Microscopy, Electron, Scanning; D009842:Oligopeptides / Q000494:pharmacology*; D010456:Peptides, Cyclic; D011817:Rabbits; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology*; D014664:Vasodilation
D015777:Eicosanoids; D009842:Oligopeptides; D010456:Peptides, Cyclic; C060347:lanreotide; D016718:Arachidonic Acid; D013004:Somatostatin; D000109:Acetylcholine