Kinins mediate the antiproliferative effect of ramipril in rat carotid artery.
Angiotensin-converting enzyme (ACE) inhibitors have been shown to inhibit neointimal proliferation in response to endothelial injury in the rat carotid artery. Since ACE inhibitors block degradation of kinins, our objective in this study was to determine whether kinins mediate the antiproliferative effect of the ACE inhibitor ramipril. Endothelial denudation was achieved in the left carotid artery of male Sprague-Dawley rats using a balloon catheter. The rats were divided into four groups: a) vehicle (saline); b) DuP 753 10 mg/kg/day; c) ramipril 5 mg/kg/day; and d) ramipril 5 mg/kg/day plus Hoe 140 70 micrograms/kg/day. Ramipril markedly reduced neointimal proliferation compared to control (vehicle) (p less than 0.05) and DuP 753-treated groups (p less than 0.05). When ramipril was given together with Hoe 140 its effect was significantly blunted (p less than 0.05). These results show that kinins are important mediators in the antiproliferative effect of ACE inhibitors.
Farhy
R D
RD
Department of Medicine, Henry Ford Hospital, Detroit, MI 48202.
Ho
K L
KL
Carretero
O A
OA
Scicli
A G
AG
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000031:analogs & derivatives; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D002339:Carotid Arteries / Q000166:cytology* / Q000187:drug effects; D020212:Carotid Artery Injuries; D004730:Endothelium, Vascular / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology*; D007705:Kinins / Q000502:physiology*; D019808:Losartan; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000293:injuries; D009842:Oligopeptides / Q000494:pharmacology; D017257:Ramipril; D051381:Rats; D011919:Rats, Inbred Strains; D013777:Tetrazoles / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D001643:Bridged Bicyclo Compounds; D007093:Imidazoles; D007705:Kinins; D009842:Oligopeptides; D013777:Tetrazoles; D000804:Angiotensin II; C065679:icatibant; D019808:Losartan; D017257:Ramipril; D001920:Bradykinin