Effects of cyclosporine A on the regenerating endothelium following direct arterial injury

Abstract

Cyclosporine A (CyA) is still considered the immunosuppressive drug of choice in human solid organ transplantation, although significant adverse side effects such as systemic hypertension and nephrotoxicity have been reported with its use. Experimentally, CyA has been reported to increase renal release of endothelin and thromboxane and also to enhance sensitivity to circulating catecholamines. Human histologic studies have shown that vessels of transplanted organs could be colonized with recipient endothelial cells suggesting a posttransplant regenerating process. Experimental models have demonstrated that regenerated endothelium does not resume its initial vasoactive characteristics but, rather, displays an increased tendency to cause vasospasm. Chronic use of CyA has also been reported to interfere with endothelial release of nitric oxide (NO). Therefore, the association of endothelial regeneration and CyA exposure as seen after an episode of acute rejection could alter the vascular reactivity of the graft and perhaps contribute to early coronary arteriosclerosis seen among heart transplant recipients. The purpose of this experiment was to study the effects of oral administration of CyA on endothelium-dependent and independent relaxation of regenerated rat thoracic aorta.