Nitric oxide (NO)-generating vasodilators inhibit the mitogenesis and
proliferation of cultured vascular smooth muscle cells. We investigate
d the role of NO in the vascular response to arterial injury by admini
stering L-arginine (precursor of NO), D-arginine or N-nitro L-arginine
methylester(NAME; an inhibitor of NO synthesis) to a rat model of bal
loon catheter-induced left carotid artery injury. Two weeks after the
balloon injury, animals that received both oral (1.25g/l water) and lo
cal (10mg in gel) administration of L-arginine showed suppression of n
eointimal proliferation with no change in systolic blood pressure. Med
ial proliferation was potentiated in NAME-treated animals with a highe
r blood pressure. Tissue cGMP content (representative of NO generation
) of the injured arteries was similar to that of normal arteries with
intact endothelium. These findings suggest that a higher local concen
tration of NO produced from L-arginine can inhibit the migration and p
roliferation of smooth muscle cells in the injured vascular wall.