title: Inhibitory effects of alprostadil (prostaglandin E1) incorporated in lipid microspheres of soybean oil on intimal hyperplasia following balloon injury in rabbits.
abstract: The present study was performed to assess the inhibitory effects of alprostadil (CAS 745-65-3, prostaglandin E1, PGE1) incorporated in lipid microspheres (here-in-after referred to as lipo PGE1; Palux inj.) on intimal thickening following balloon injury in the carotid artery of normal rabbits. Lipo PGE1 was given intravenously to animals twice a day at doses of 20 or 40 micrograms/kg/day from ballooning (day 1) until day 3, and at half these doses from day 4 to day 20. The carotid artery was removed for histopathological staining on the next day (day 21) after the last administration. Lipo PGE1 significantly reduced both the intimal/medial are (I/M) ratio and stenosis ratio by about half in the 40 micrograms/kg/day on day 21 after ballooning, compared with the vehicle group. Infiltration of macrophage, expression of proliferating cell nuclear antigen (PCNA)-positive cells was inhibited by the administration of lipo PGE1 on day 3 after ballooning. Adhesion of platelets to injured arterial walls was also inhibited on day 3. Lipo PGE1 at 40 micrograms/kg/day exerted more potent inhibitory effects on I/M and stenosis ratios and histopathological changes such as infiltration of macrophage and expression of PCNA-positive cells than at 20 micrograms/kg/day. These findings suggest that lipo PGE1 inhibits the intimal hyperplasia after balloon injury in rabbit carotid artery, possibly by inhibiting platelet functions.
authors.affiliation: Department of Pharmacology, Haruna Research Laboratories, Nippon Experimental Medical Research Institute Co., Ltd., Agatsuma, Gunma, Japan.
authors.forename: Mineo
authors.initials: M
authors.lastname: Kunihara
authors.forename: Katsuharu
authors.initials: K
authors.lastname: Tsuchida
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Kaneko
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Suga
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Saeri
authors.initials: S
authors.lastname: Mochizuki
authors.forename: Keiko
authors.initials: K
authors.lastname: Kawai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shiga
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamaguchi
mesh_terms: D000527:Alprostadil / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D020212:Carotid Artery Injuries / Q000473:pathology*; D002404:Catheterization; D006965:Hyperplasia / Q000209:etiology / Q000473:pathology; D007150:Immunohistochemistry; D008055:Lipids; D008297:Male; D008854:Microscopy, Electron; D008863:Microspheres; D011817:Rabbits; D013024:Soybean Oil
chemical_list: D008055:Lipids; D013024:Soybean Oil; D000527:Alprostadil