Six I, Van Belle E, Bordet R, Corseaux D, Callebert J, Dupuis B, Bauters C, Bertrand M E
Department of Pharmacology, University of Lille, France.
Cardiovasc Res. 1999 Aug 15;43(3):731-8. doi: 10.1016/s0008-6363(99)00113-3.
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.
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.
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).
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.