Different contribution of apoptosis to the antiproliferative effects of L-arginine, enalapril and losartan on neointimal growth inhibition after balloon arterial injury.
It remains to be clarified how angiotensin-converting enzyme inhibitor-induced function (ie, increased NO related action or the inhibition of angiotensin II AT1 receptor dependent action) affects apoptosis of smooth muscle cells in the neointima following arterial injury. Saline (control), enalapril, L-arginine, combined enalapril and L-arginine, or losartan was administered for 14 days to Sprague-Dawley rats after balloon carotid injury and the ratio of intima to media areas (I/M), inducible NO synthase (iNOS) concentrations and %TUNEL were measured. I/M decreased similarly in the enalapril, L-arginine and losartan groups, and the combination of enalapril and L-arginine resulted in the largest I/M decrease. TUNEL positivity was increased compared with controls in the following order: losartan, L-arginine, enalapril and combination of enalapril and L-arginine. The intensity of immunostaining for iNOS was increased approximately 1.9-fold compared with the control in the combined enarapril and L-arginine group as well as in the enalapril group. These data suggest that the apoptosis in the neointima is different for L-arginine, losartan and enalapril under similar conditions and was higher under treatment with enalapril, not only via the action of NO or blocking of the AT1, but also by upregulation of iNOS.
Ohwada
Takayuki
T
First Department of Internal Medicine, Fukushima Medical University, Japan.
Ishibashi
Toshiyuki
T
Yaoita
Hiroyuki
H
Shindo
Joji
J
Noji
Hideyoshi
H
Ohkawara
Hiroyuki
H
Sugimoto
Kouichi
K
Sakamoto
Takayuki
T
Maehara
Kazuhira
K
Maruyama
Yukio
Y
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001120:Arginine / Q000494:pharmacology; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000209:etiology; D002404:Catheterization / Q000009:adverse effects; D002455:Cell Division / Q000187:drug effects; D004656:Enalapril / Q000494:pharmacology; D006083:Graft Occlusion, Vascular / Q000188:drug therapy*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019808:Losartan