ABSTRACT
Interleukin-2 (IL-2) therapy often results in potentially life-threatening side effects including hypotension. However, the mechanism has not been completely elucidated. In order to determine whether IL-2 modifies vascular tone, we investigated the effect of IL-2 on rat thoracic aorta rings and the underlying mechanisms. Effects of IL-2 on the contraction of high KCl and phenylephrine (PE) preconstricted rat thoracic aorta with or without endothelium were determined by organ bath technique. To explore the mechanism, nitric oxide synthase inhibitor L-N(G)-nitroarginine methyl ester (L-NAME), guanylyl cyclase inhibitor methylene blue, and cyclooxygenase inhibitor indomethacin were used. IL-2 (10-1000 U/ml) caused concentration-dependent relaxation of aorta rings preconstricted with PE (10 micromol/L) in endothelium-intact rings, but had no effect on KCl (120 mmol/L) preconstricted rings. Removal of the endothelium, or pretreatment with L-NAME (0.1 mmol/L) or methylene blue (10 micromol/L) or indomethacin (10 micromol/L), inhibited the relaxation of IL-2. The results indicate that the relaxation by IL-2 in rat aorta ring is endothelium-dependent and is possibly mediated by the NO-guanylyl cyclase pathway and cyclooxygenase-dependent pathway.