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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1926.)
© 2007 American Heart Association, Inc.

Vascular Biology

Endothelial Nitric Oxide Synthase Activity Is Essential for Vasodilation During Blood Flow Recovery but not for Arteriogenesis

Barend Mees; Shawn Wagner; Elena Ninci; Silvia Tribulova; Sandra Martin; Rien van Haperen; Sawa Kostin; Matthias Heil; Rini de Crom; Wolfgang Schaper

From the Department of Experimental Cardiology (S.W., E.N., S.T., S.M., S.K., M.H., W.S.), Max-Planck-Institute for Heart & Lung Research, Bad Nauheim, Germany; and the Departments of Cell Biology & Genetics (B.M., R.v.H., R.d.C.) and Vascular Surgery (B.M., R.d.C.), Erasmus University MC, Rotterdam, The Netherlands.

Correspondence to Barend M.E. Mees, MD, Department of Cell Biology & Genetics, Erasmus University MC Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. E-mail b.mees{at}erasmusmc.nl

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.

Methods and 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.

We evaluated collateral artery growth in 3 mouse strains with different eNOS expression (eNOS-deficient, eNOS-overexpressing, and wild-type mice) using a distal femoral artery ligation model. We demonstrate that eNOS activity is crucial for NO-mediated vasodilation of peripheral collateral vessels after arterial occlusion, but not for collateral artery growth.

Key Words: endothelial nitric oxide synthase • arteriogenesis • mouse • hind limb • vasodilation

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