Role of nitric oxide in the effect of blood flow on neointima formation.
OBJECTIVE
Neointima formation after arterial injury is inhibited by increased blood flow. The object of this study was to determine whether nitric oxide mediates the effect of increased blood flow on neointima formation.


METHODS
Balloon catheter-denuded rat carotid arteries were exposed to increased blood flow or control blood flow by ligation of the contralateral carotid artery. Beginning 2 days before balloon denudation, rats were given either saline vehicle alone or the nitric oxide synthase inhibitor N-nitro-L-arginine-methyl ester (L-NAME) at a dose of 10 mg/kg/day or 2 mg/kg/day intraperitoneally. The normalized neointima area was measured 14 days after denudation.


RESULTS
Blood flow was significantly increased by ligation of the contralateral carotid artery for all drug treatments (p<0.008). In rats given saline vehicle only, normalized neointima area was significantly reduced after increased blood flow compared with control blood flow (0.33+/-0.04 compared with 0.48+/-0.03; p=0.006). Systolic blood pressure was significantly elevated by treatment with high-dose L-NAME (p=0.002 compared with vehicle), but was not altered by low-dose L-NAME (p=NS compared with vehicle). Normalized neointima area was not significantly reduced after increased carotid blood flow for rats treated with either dose of L-NAME (p=NS).


CONCLUSIONS
The inhibition of neointima formation by increased blood flow was abolished with hypertensive and nonhypertensive doses of the nitric oxide synthase inhibitor L-NAME, which suggests that the L-NAME effects are independent of systemic hemodynamic alterations. It is concluded that flow-induced inhibition of neointima formation is mediated in part by nitric oxide.
Ellenby
M I
MI
Division of Vascular Surgery, Henry Ford Hospital, Detroit, Mich., 48202, USA.
Ernst
C B
CB
Carretero
O A
OA
Scicli
A G
AG
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology*; D020212:Carotid Artery Injuries; D002404:Catheterization / Q000009:adverse effects / Q000295:instrumentation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018056:Hemorheology; D007274:Injections, Intraperitoneal; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D012965:Sodium Chloride; D017539:Tunica Intima / Q000187:drug effects / Q000293:injuries / Q000473:pathology*
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D012965:Sodium Chloride; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester