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Objective: Growth regulatory properties of nitric oxide (NO) in cultured endothelial cells is controversial. The aim of our study was to investigate the effect of l-arginine, the endogenous NO precursor, and l-NAME, an inhibitor of NO synthase on the reendothelialization process after angioplasty. Methods: Fifty-five New Zealand White rabbits underwent denudation of the left iliac artery. After injury the rabbits were randomized in three groups: l-arginine 2.25% (l-arginine, n=19); NG-nitro-l-arginine methyl ester 15 mg/kg/day (l-NAME, n=19); and placebo (controls, n=17). Treatment was solubilized in drinking water. Reendothelialization was evaluated at 4 weeks by macroscopic evaluation of Evans blue staining and endothelial-specific immunostaining (CD-31) on cross sections. Intimal hyperplasia was evaluated by morphometric analysis. Results: Despite a significant increase in plasma arginine (P=0.001) and a reduction in intimal hyperplasia (P=0.003) with l-arginine, neither agent had a significant effect on reendothelialization at 4 weeks (controls=36±4%, l-arginine=43±3%, l-NAME=33±4%; NS). Conclusion: These results suggest that, in spite of previously demonstrated effects on neointimal hyperplasia, the NO pathway does not influence the regrowth of macrovascular endothelial cells in vivo. [ABSTRACT FROM PUBLISHER]