Enhanced nitric oxide production induced by the administration of L-arginine does not inhibit arterial neointimal formation after overwhelming alloimmune injury.
BACKGROUND
Nitric oxide suppresses proliferation and function of T cells and inhibits proliferation of smooth muscle cells in vitro and in vivo. The purpose of this study was to determine whether nitric oxide, stimulated by means of the oral administration of L-arginine, would reduce the degree of intimal thickening produced by immune injury in rat arterial allografts.


METHODS
Orthotopic femoral artery transplantation was done with Brown Norway donors and Lewis recipients. Seven days before operation, and for 39 additional days, one group received 2.25% L-arginine and one group received 0.01% N-omega-nitro-L-arginine in tap water; one group received tap water only. Forty days after operation, all arterial segments were excised and examined by histopathologic, morphometric, and immunohistochemical assays.


RESULTS
There was no difference in the rejection response or degree of intimal thickening among the three groups. There were no qualitative differences in numbers of T cells, macrophages, or smooth muscle cells in the neointima, media, or adventitia among the untreated and treated groups. Induced nitric oxide synthase was present in the media and adventitia of the allograft vessels, but not in native rat arteries.


CONCLUSIONS
Enhanced production of nitric oxide, via the administration of L-arginine, has been shown to reduce tissue pathologic changes in models of mechanical or dietary injury. Enhanced nitric oxide production did not suppress rejection or inhibit intimal thickening in this model of immune-mediated injury.
Gregory
C R
CR
Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis 95616-8745, USA.
Cooke
J P
JP
Patz
J D
JD
Berryman
E R
ER
Shorthouse
R
R
Morris
R E
RE
D000284:Administration, Oral; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology*; D005263:Femoral Artery / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D007150:Immunohistochemistry; D008297:Male; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous; D017539:Tunica Intima / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase