L-arginine inhibits neointimal formation following balloon injury

Abstract

Nitric oxide (NO)-generating vasodilators inhibit the mitogenesis and proliferation of cultured vascular smooth muscle cells. We investigated the role of NO in the vascular response to arterial injury by administering L-arginine (precursor of NO), D-arginine or N-nitro L-arginine methylester (NAME; an inhibitor of NO synthesis) to a rat model of balloon catheter-induced left carotid artery injury. Two weeks after the balloon injury, animals that received both oral (1.25g/l water) and local (10mg in gel) administration of L-arginine showed suppression of neointimal proliferation with no change in systolic blood pressure. Medial proliferation was potentiated in NAME-treated animals with a higher 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 concentration of NO produced from L-arginine can inhibit the migration and proliferation of smooth muscle cells in the injured vascular wall.