Regional differences in vasculotoxic effects of cyclosporin in rats

Studies on cyclosporin-induced vasculotoxicity often yielded discrepant results, possibly as a result of differences in study protocols. The aim of the present study was to analyse cyclosporin-induced vasculotoxicity in arteries of different size and origin. Therefore, rats were treated with cyclosporin, 20 mg.kg-1.day-1, by gastric gavage for 10 days. In our previous studies, this treatment schedule induced renal functional impairment in vivo and an impaired relaxation response of thoracic aortic rings in vitro. Relaxation of various arteries (thoracic and abdominal aorta and carotid, renal, and interlobar arteries) from cyclosporin-treated and control rats in response to endothelium-dependent and -independent vasodilators was analysed. The thoracic aorta showed diminished endothelium-dependent and -independent relaxations; in the abdominal aorta no impairment was observed. Moreover, the dysfunction of the thoracic aorta seemed to be homogeneous along its length and showed an abrupt termination at the level of the diaphragm. In all other segments studied, no impairment of the relaxation responses was found. A similar pattern of vascular damage was found in rats treated with a very toxic cyclosporin treatment (50 mg.Kg-1.day-1 s.c. x 7 days). The results indicate regional differences in cyclosporin-induced vasculotoxicity. The thoracic aorta, and in view of the fall of the renal blood flow, most likely also the renal resistance vessels, could be more susceptible than other vessels to cyclosporin-induced vascular dysfunction.