Interleukin-2 induced endothelium-dependent relaxation of rat thoracic aorta

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 μmol/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 μmol/L) or indomethacin (10 μmol/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.