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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:767-776.)
© 1999 American Heart Association, Inc.

Original Contributions

Continuous Perivascular L-Arginine Delivery Increases Total Vessel Area and Reduces Neointimal Thickening After Experimental Balloon Dilatation

Johan M. Bosmans; Chris J. Vrints; Mark M. Kockx; Hidde Bult; Kristel M. C. Cromheeke; Arnold G. Herman

From the Department of Cardiology (J.M.B., C.J.V., K.M.C.C.) and Pharmacology (H.B., A.G.H.), University of Antwerp (UIA), Wilrijk, Belgium; and the Department of Pathology, AZ Middelheim, Antwerp, Belgium (M.M.K.).

Correspondence to Johan Bosmans, MD, PhD, University Hospital Antwerp (UZA), Department of Cardiology, Wilrijkstraat 10, 2650 Edegem, Belgium.

Abstract—The aim of this study was to evaluate whether vascular remodeling and neointimal thickening occur after balloon dilatation of the nonatherosclerotic rabbit carotid artery, and whether both processes are influenced by continuous perivascular delivery of L-arginine or the nitric oxide synthase inhibitor N^G-nitro-L-arginine methyl ester (L-NAME). In the first experiment, histological and morphometric evaluation of arteries was performed at different time points after balloon dilatation: 10 minutes (n=7), and 1 (n=7), 2 (n=9), 3 (n=20), or 10 (n=5) weeks. Neointimal thickening progressively contributed to luminal narrowing for at least 10 weeks after angioplasty. During the first 2 weeks after dilatation, a significant decrease of the total vessel area was measured. Ten weeks after dilatation, both the neointimal and total vessel area were increased without further changing of the luminal area. In the second experiment, endothelial injured rabbits were randomly assigned to receive 2 weeks of continuous local perivascular physiological salt solution (n=6), L-arginine (n=8), or L-NAME (n=7), starting immediately after balloon dilatation (ie, local drug delivery during the first phase of the biphasic vascular remodeling process). Perivascular L-arginine delivery significantly reduced the neointimal area, despite an increased number of neointimal Ki-67-positive smooth muscle cells. Both the luminal area and total vessel area were significantly increased. Serum L-arginine levels remained unchanged. L-NAME administration had no effect on the neointimal area, nor on the luminal and total vessel area. Neointimal formation and biphasic vascular remodeling occur after experimental balloon dilatation of the nonatherosclerotic rabbit carotid artery, and can be influenced by continuous local perivascular delivery of L-arginine.

Key Words: balloon dilatation • neointima • remodeling • restenosis • nitric oxide • L-arginine

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