Flow-induced arterial enlargement is inhibited by suppression of nitric oxide synthase activity in vivo.
BACKGROUND
Acute flow-induced arterial dilation is mediated by nitric oxide (NO). The role of NO in chronic flow-induced adaptive enlargement is unknown. We assessed the role of NO in arterial adaptation to increased blood flow (BF).


METHODS
Iliac artery BF was increased in adult male rats by creating a left femoral arteriovenous fistula. Left iliac BF and diameter were measured, and wall shear stress was calculated. The effect of the NO synthase inhibitor N omega-nitro-L-arginine-methyl ester (L-NAME) was studied in arteriovenous fistula rats divided into three groups (group 1, vehicle, group 2, 0.5 mg/ml; group 3, 2 mg/ml) in drinking water. Arterial diameter, blood pressure, and medial cell density were assessed after 21 days. Left iliac cyclic guanosine monophosphate content was measured in an additional group of animals.


RESULTS
BF and wall shear stress in the left iliac artery increased fourfold immediately after arteriovenous fistula. Arterial enlargement was evident after 7 days, and wall shear stress normalized after 42 days. Flow-induced arterial enlargement was inhibited by both low- and high-dose L-NAME compared with control (analysis of variance p < 0.05). Blood pressure was elevated only in animals treated with high-dose L-NAME. Left iliac cyclic guanosine monophosphate content was lower in rats treated with L-NAME than in the control group (p < 0.05).


CONCLUSIONS
NO suppression by L-NAME inhibits flow-induced iliac artery enlargement in rats. This finding suggests that NO plays a role in flow-induced arterial remodeling.
Guzman
R J
RJ
Department of Surgery, Stanford University Medical Center, Calif. 94305, USA.
Abe
K
K
Zarins
C K
CK
D000818:Animals; D001164:Arteriovenous Fistula; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D007083:Iliac Artery / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013314:Stress, Mechanical; D013997:Time Factors; D017540:Tunica Media / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester