THE NITRIC-OXIDE PRECURSOR L-ARGININE REDUCES EXPRESSION OF HYALURONAN SYNTHASE IN EXPERIMENTAL VEIN BYPASS GRAFTS

Background. The success of vascular bypass procedures is limited by th e development of intimal hyperplasia (IH). The nitric oxide (NO) precu rsor, L-arginine (L-ARG) significantly reduces IH in both arteries and experimental vein grafts; however, the precise mechanism has yet to b e elucidated. Hyaluronan synthase-1 (HAS-1) is one of the two enzymes believed to be responsible for making hyaluronan, a key component extr acellular matrix composition. Purpose. To determine how L-ARG; supplem entation affects the gene expression of HAS-1 in experimental vein gra fts. Methods. Thirty-four male New Zealand white rabbits were divided into three groups: control (no operation, regular chow and water, n = 4); L-ARG supplemented (n = 15); and no L-ARG (n = 15), The latter two groups underwent a right interposition carotid bypass using jugular v ein, Vein grafts were harvested at 7, 14, and 21 days after surgery. R ibonuclease protection assays were performed using P-32-labeled ribopr obes for HAS-1 and 188 rRNA as an internal control and expressed as a ratio (HAS-1/rRNA). Results. There was a significant rise in HAS-1 exp ression in the vein grafts 7 (1.57 +/- 0.5), 14 (0.7 +/- 0.2), and 21 days (2.82 +/- 0.7) after grafting compared to control (0.14 +/- 0.08) (P < 0.05), L-ARG-supplemented animals had a significant decrease in HAS-1 expression at 21 days (0.65 +/- 0.1) compared to nonsupplemented vein grafts (2.82 +/- 0.7) CP < 0.02). Conclusions. These results dem onstrate for the first time a significant rise in HAS expression in th e early experimental vein grafts. Furthermore, L-ARG; supplementation significantly diminishes the expression of HAS at 21 days. These resul ts may represent a potential mechanism by which augmentation of the L- ARG/NO pathway inhibits IH in experimental vein grafts and may ultimat ely provide for improved therapeutic interventions in alleviating IH. (C) 1998 Academic Press.