[Effects of amrinone, an inhibitor of c-AMP-specific phosphodiesterases, on neointimal hyperplasia after balloon injury in rats].
Amrinone(5-amino(3,4'-bibyridin)6-(1H)-one), an inhibitor of c-AMP-specific phosphodiesterases, has been used clinically as an inodilator. We have investigated the effect of amrinone on neointimal hyperplasia in rat carotid artery after balloon injury. When amrinone was administered subcutaneously to rats at a dose of 10 mg/kg/day for 14 days, significant reduction of neointimal thickness was noted. Four days treatment with amrinone, however, failed to reduce the intimal thickness. To investigate the mode of action to reduce intimal thickness, we tried to study the effects of amrinone on platelet aggregation and the proliferation of aortic smooth muscle cells. Amrinone produced a dose-dependent inhibition of ADP-induced rat platelet aggregation in vitro as well as ex vivo in rats. The proliferation of human aortic smooth muscle cells in culture stimulated with FBS or PDGF was also inhibited by amrinone. These results indicate that amrinone may have potential to prevent vascular neointimal hyperplasia in clinical balloon injury through inhibition of vascular smooth muscle cell growth and platelet aggregation.
Hachisu
M
M
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., Yokohama, Japan.
Nomura
M
M
Fujishima
K
K
D000676:Amrinone / Q000494:pharmacology*; D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology; D020212:Carotid Artery Injuries; D002404:Catheterization / Q000009:adverse effects*; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D006965:Hyperplasia; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000187:drug effects*
D010726:Phosphodiesterase Inhibitors; D010975:Platelet Aggregation Inhibitors; D000676:Amrinone