Endothelial nitric oxide synthase activity is essential for vasodilation during blood flow recovery but not for arteriogenesis.
OBJECTIVE
Arteriogenesis is the major mechanism of vascular growth, which is able to compensate for blood flow deficiency after arterial occlusion. Endothelial nitric oxide synthase (eNOS) activity is essential for neovascularization, however its specific role in arteriogenesis remains unclear. We studied the role of eNOS in arteriogenesis using 3 mouse strains with different eNOS expression.


RESULTS
Distal femoral artery ligation was performed in eNOS-overexpressing mice (eNOStg), eNOS-deficient (eNOS-/-) mice, and wild type (WT) controls. Tissue perfusion and collateral-dependent blood flow were significantly increased in eNOStg mice compared with WT only immediately after ligation. In eNOS-/- mice, although tissue perfusion remained significantly decreased, collateral-dependent blood flow was only decreased until day 7, suggesting normal, perhaps delayed collateral growth. Histology confirmed no differences in collateral arteries of eNOStg, eNOS-/-, and WT mice at 1 and 3 weeks. Administration of an NO donor induced vasodilation in collateral arteries of eNOS-/- mice, but not in WT, identifying the inability to vasodilate collateral arteries as main cause of impaired blood flow recovery in eNOS-/- mice.


CONCLUSIONS
This study demonstrates that eNOS activity is crucial for NO-mediated vasodilation of peripheral collateral vessels after arterial occlusion but not for collateral artery growth.
Mees
Barend
B
Department of Cell Biology & Genetics, Erasmus University MC Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. b.mees@erasmusmc.nl
Wagner
Shawn
S
Ninci
Elena
E
Tribulova
Silvia
S
Martin
Sandra
S
van Haperen
Rien
R
Kostin
Sawa
S
Heil
Matthias
M
de Crom
Rini
R
Schaper
Wolfgang
W
D000818:Animals; D003097:Collateral Circulation / Q000502:physiology; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000293:injuries; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D014664:Vasodilation / Q000502:physiology*
D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse