PYRROLIDINE DITHIOCARBAMATE SELECTIVELY PREVENTS THE EXPRESSION OF THE INDUCIBLE NITRIC-OXIDE SYNTHASE IN THE RAT AORTA

Exposure of rat aortic rings without endothelium to interleukin-1 beta for 5 h significantly attenuated the contractions due to phenylephrin e and increased the tissue content of guanosine 3',5'-cyclic monophosp hate (cyclic GMP) due to the induction of nitric oxide synthase. The p resence of pyrrolidine dithiocarbamate, a specific inhibitor of nuclea r transcription factor kappa B activation, during the exposure of the rings to interleukin-1 beta prevented these responses to interleukin-1 beta. Rat aortic rings which had been incubated for 5 h with interleu kin-1 beta in the absence and presence of pyrrolidine dithiocarbamate prior to the organ chamber experiment had a similar concentration-depe ndent relaxation curve for acetylcholine in rings with endothelium, an d for 3-morpholino-sydnonimine (SIN-1) in rings without. Pyrrolidine d ithiocarbamate applied acutely did not alter the tone elicited by phen ylephrine in rings with or without endothelium and had no effect on th e subsequent relaxation induced by acetylcholine in rings with endothe lium or by SIN-1 in rings without endothelium. These observations sugg est that pyrrolidine dithiocarbamate prevents the interleukin-1 beta-m ediated expression of the inducible nitric oxide synthase without affe cting the activity of the constitutive enzyme in the rat aorta.