Endothelial Nitric Oxide Synthase Deficiency Enhanced Carotid Artery Ligation-Induced Remodeling by Promoting Vascular Inflammation

Nitric oxide (NO) plays an important role in vascular protection. It has been reported that endothelial NO synthase (eNOS) deficiency exacerbated carotid artery ligation (CAL)-induced vascular remodeling, which, however, did not elucidate the role of inflammation. Overexpression of eNOS inhibited vascular inflammation and remodeling in a CAL model. However, there is no study that tested the hypothesis that eNOS deficiency can enhance the inflammatory 100 response that plays a critical role in exacerbation of CAL-induced vascular remodeling. Thus, the present study used both eNOS knockout (eNOS-KO) mice and pharmacological blockade of nitric oxide synthase (NOS) to examine the temporal relationship between the inflammatory process and vascular remodeling by CAL and how elimination of NO production affects this. The left common carotid artery was ligated in eNOS-KO, or wild type (WT) mice treated with or without an NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). In WT mice, CAL induced vascular inflammation, characterized by neutrophil and macrophage infiltration into the vessel wall at 1 week. Although the inflammation diminished at 4 weeks, the ligated carotid artery developed prominent vascular The Journal of Applied Research • Vol. 6, No. 1, 2006 Endothelial Nitric Oxide Synthase Deficiency Enhanced Carotid Artery Ligation-Induced Remodeling by Promoting Vascular Inflammation Le-ning Zhang, PhD* Valdeci da Cunha, PhD† Baby Martin-McNulty, BS† Dennis Wilson, PhD†† Mark E. Sullivan, PhD† Ronald Vergona, PhD† John C. Rutledge, MD* Yi-Xin Wang, MD† *Department of Internal Medicine, School of Medicine, University of California at Davis, Davis, California †Department of Pharmacology, Berlex Biosciences, Richmond, California ‡Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California at Davis, Davis, California