REGIONAL DIFFERENCES IN VASCULOTOXIC EFFECTS OF CYCLOSPORINE IN RATE

Studies on cyclosporin-induced vasculotoxicity often yielded discrepan t results, possibly as a result of differences in study protocols. The aim of the present study was to analyse cyclosporin-induced vasculoto xicity in arteries of different size and origin. Therefore, rats were treated with cyclosporin, 20 mg . kg(-1). day(-1), by gastric gavage f or 10 days. In our previous studies, this treatment schedule induced r enal functional impairment in vivo and an impaired relaxation response of thoracic aortic rings in vitro. Relaxation of various arteries (th oracic 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 ao rta showed diminished endothelium-dependent and -independent relaxatio ns; in the abdominal aorta no impairment was observed. Moreover, the d ysfunction of the thoracic aorta seemed to be homogeneous along its le ngth and showed an abrupt termination at the level of the diaphragm. I n all other segments studied, no impairment of the relaxation response s was found. A similar pattern of vascular damage was found in rats tr eated with a very toxic cyclosporin treatment (50 mg . kg(-1). day(-1) s.c. x 7 days). The results indicate regional differences in cyclospo rin-induced vasculotoxicity. The thoracic aorta, and in view of the fa ll of the renal blood flow, most likely also the renal resistance vess els, could be more susceptible than other vessels to cyclosporin-induc ed vascular dysfunction.