FUNCTIONAL-ANALYSIS OF VASCULAR DYSFUNCTION IN CYCLOSPORINE-TREATED RATS

Objective: The aim was to analyse vascular damage after chronic cyclos porin treatment (20 mg.kg(-1) during 10 d) in rats. Methods: The react ivity to different vasoactive agents was studied on thoracic aortic ri ngs from control rats, and from rats subjected to renal ablation or cy closporin treatment. Results: After cyclosporin treatment the endothel ium dependent vasodilator responses to acetylcholine and to the endoth elium independent NO donors were suppressed. These defects were restor ed after a 7 d recovery period. The contractile response after inhibit ion of basal endothelial NO synthesis was unaffected. Further analysis of the blunted vasodilatations not only points to impairments of cGMP mediated mechanisms but shows that other pathways are possibly involv ed as well. Renal insufficiency induced by renal mass reduction did no t influence the aortic reactivity. Conclusions: Cyclosporin induced va sculotoxicity is a reversible phenomenon, and is not due to renal dysf unction as such. It seems to provoke a defect in the vasodilator mecha nisms at the level of the vascular smooth muscle cells and most likely no impairment of endothelial nitric oxide production.