Effect of intracoronary L-NAME infusion on endothelial dysfunction and intimal hyperplasia after heart transplantation

Abstract

The present study was designed to examine the effect of nitric oxide synthase inhibition on coronary endothelial dysfunction and the development of accelerated atherosclerosis after heart transplantation. A porcine model was used to study the effect of inhibition of endothelial nitric oxide synthase by intracoronary L-Nitro Arginine Methyl Ester (L-NAME; 1 mg/kg/day) infusion by an osmotic pump on these two end-points. The endothelium-dependent relaxations of allografted epicardial coronary arteries, allografted arteries infused with L-NAME, allografted arteries mounted with the pump and vehicle and native coronary arteries were compared 30 days after graft implantation using standard organ chamber experiments. Intimai thickening was measured by light microscopy examination using a semiquantitative scale (0 to 4+ grading). There was a significant decrease of relaxations to serotonin in allografted arteries infused directly with L-NAME compared with allografted arteries from swines receiving the drug. There was a significant increase in the prevalence and severity of intimai thickening in allografted coronary arteries infused with L-NAME compared to allografts without infusion (prevalence: 100%, grade 3-4+ lesions 37.5%, and prevalence: 46.6%, grade 3-4 lesions: 0% respectively). Inhibition of the nitric oxide pathway accelerates the intimai thickening process leading to graft coronary vasculopathy.