A selective somatostatin type-2 receptor agonist inhibits neointimal thickening and enhances endothelial cell growth and morphology following aortic balloon injury in the rabbit.
Somatostatin analogs have been shown to inhibit vascular smooth muscle cell (VSMC) proliferation and attenuate neointimal thickening following experimental balloon catheter injury. In this study, the effects of a selective agonist for the somatostatin receptor subtype 2, PRL-2486, on neointimal thickening and endothelial cell regrowth 2 weeks following balloon catheterization of male New Zealand White rabbits were determined. Rabbits treated 2 days prior to and 2 weeks after catheter injury with 10 microg/kg/day PRL-2486 (PRL-tx) had decreased I/M ratios (intimal area/medial area x 100; p < 0.05) but had no effect at lower (5 microg/kg/day) or higher (20 microg/kg/day) doses. PRL-tx had significantly decreased VSMC proliferation compared to untreated animals. PRL-tx increased endothelial regrowth by over 2-fold (p < 0.002) and improved endothelial cell morphology. Endothelial-dependent relaxation responses to acetylcholine were attenuated by catheter injury, and were not improved with PRL-tx. These data suggest that the PRL-2486-mediated inhibition of neointimal thickening exhibits a bell-shaped dose-response curve. This inhibition may be due in part to decreased VSMC proliferation, which may be a function of enhanced endothelial regrowth, but not the return of endothelium-dependent vascular function.
Schiller
Natalie K
NK
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Timothy
Alvin M
AM
Aurora
Harmeet S
HS
Chen
I-Li
IL
Coy
David H
DH
Murphy
William A
WA
Akers
Donald L
DL
Fonseca
Vivian A
VA
Kadowitz
Philip J
PJ
McNamara
Dennis B
DB
D000818:Animals; D001011:Aorta / Q000293:injuries / Q000473:pathology / Q000648:ultrastructure; D002404:Catheterization / Q000009:adverse effects*; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000293:injuries / Q000473:pathology*; D008297:Male; D008854:Microscopy, Electron; D011817:Rabbits; D017481:Receptors, Somatostatin / Q000819:agonists*; D012680:Sensitivity and Specificity; D017539:Tunica Intima / Q000187:drug effects / Q000293:injuries / Q000473:pathology*
D017481:Receptors, Somatostatin; C093733:somatostatin receptor 2