REPEATED ENDOTHELIAL REMOVAL AUGMENTS INTIMAL THICKENING AND ATTENUATES EDRF RELEASE

To evaluate the significance of repeated denudation injury in progress ion of atherosclerosis, we performed a single and then a second balloo n denudation on the rabbit carotid arteries. Morphological examination s and organ chamber experiments were performed, and the results were c ompared. On morphological examinations, reendothelialization was almos t completed in 2 wk after redenudation, whereas it required 6 wk after a single denudation. Intimal thickening progressed after redenudation . Organ chamber experiments showed that contractile responses and endo thelium-independent relaxation remained unchanged after redenudation. Endothelium-dependent relaxations to acetylcholine, ADP, and substance P decreased progressively by repeating denudation. These relaxation r esponses were inhibited by N-G-nitro-L-arginine, hemoglobin, and methy lene blue and were considered to be associated with the production and /or release of endothelium-derived relaxing factor-nitric oxide (EDRF- NO). The diffusion barrier mechanism for the decreased endothelium-dep endent relaxations was ruled out using sandwich experiments. In conclu sion, repeated endothelial denudation caused progression of intimal th ickening and acceleration of endothelial regeneration, and repeated en dothelial regeneration resulted in progressively less production and/o r release of EDRF-NO.