title: A selective somatostatin type-2 receptor agonist inhibits neointimal thickening and enhances endothelial cell growth and morphology following aortic balloon injury in the rabbit.
abstract: 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.
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
authors.forename: Natalie K
authors.initials: NK
authors.lastname: Schiller
authors.forename: Alvin M
authors.initials: AM
authors.lastname: Timothy
authors.forename: Harmeet S
authors.initials: HS
authors.lastname: Aurora
authors.forename: I-Li
authors.initials: IL
authors.lastname: Chen
authors.forename: David H
authors.initials: DH
authors.lastname: Coy
authors.forename: William A
authors.initials: WA
authors.lastname: Murphy
authors.forename: Donald L
authors.initials: DL
authors.lastname: Akers
authors.forename: Vivian A
authors.initials: VA
authors.lastname: Fonseca
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Kadowitz
authors.forename: Dennis B
authors.initials: DB
authors.lastname: McNamara
mesh_terms: 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*
chemical_list: D017481:Receptors, Somatostatin; C093733:somatostatin receptor 2