Continuous perivascular L-arginine delivery increases total vessel area and reduces neointimal thickening after experimental balloon dilatation

The aim of this study was to evaluate whether vascular remodeling and neoin timal thickening occur after balloon dilatation of the nonatherosclerotic r abbit carotid artery, and whether both processes are influenced by continuo us perivascular delivery of L-arginine or the nitric oxide synthase inhibit or N-G-nitro-L-arginine methyl ester (L-NAME). In the first experiment, his tological and morphometric evaluation of arteries was performed at differen t 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 contr ibuted to luminal narrowing for at least 10 weeks after angioplasty. During the first 2 weeks after dilatation, a significant decrease of the total ve ssel area was measured. Ten weeks after dilatation, both the neointimal and total vessel area were increased without further changing of the luminal a rea. In the second experiment, endothelial injured rabbits were randomly as signed to receive 2 weeks of continuous local perivascular physiological sa lt 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 deliver y significantly reduced the neointimal area, despite an increased number of neointimal Ki-67-positive smooth muscle cells. Both the luminal area and t otal vessel area were significantly increased. Serum L-arginine levels rema ined unchanged. L-NAME administration had no effect on the neointimal area, nor on the luminal and total vessel area. Neointimal formation and biphasi c vascular remodeling occur after experimental balloon dilatation of the no natherosclerotic rabbit carotid artery, and can be influenced by continuous local perivascular delivery of L-arginine.