Involvement of nitric oxide in the smooth muscle tone of the isolated canine spleen and the responses to acetylcholine and substance P.

1. The canine isolated spleen was perfused at constant flow with warmed (37 degrees C) Krebs solution while the splenic arterial perfusion pressure (SAPP) and spleen weight were recorded continuously. An augmented smooth muscle tone was maintained by a continuous intra-arterial infusion of noradrenaline (0.01-0.1 mumol min-1) throughout the experiment. 2. Intra-arterial infusion of indomethacin (5.6 microM) significantly elevated (P < 0.05) the augmented vascular tone and the subsequent infusion of L-NAME (10 microM) further raised this vascular tone significantly (P < 0.01). 3. The splenic vasoconstrictor response to L-NAME was significantly (P < 0.05) reduced by the subsequent infusion of L-arginine (300 microM) but not of D-arginine (300 microM). 4. Neither L-NAME nor D-NAME had any effect on the basal vascular tone or the spleen weight in conditions of either basal or augmented tone. 5. Bolus injection of acetylcholine, substance P, sodium nitroprusside and isoprenaline caused short-lasting reductions in the SAPP. 6. The splenic vasodilator responses to ACh and SP, but not those to SNP and ISO, were significantly (P < 0.05) reduced by the infusion of L-NAME (10 microM), methylene blue (30 microM) but not of D-NAME (10 microM). 7. The reductions in the vasodilator responses to ACh and SP caused by L-NAME were partially reversed by L-arginine (300 microM), but not by D-arginine (300 microM). 8. The results demonstrate the contribution of nitric oxide (NO) release to the maintenance of the augmented splenic vascular tone and also the contribution of NO to the splenic vasodilator responses to ACh and SP.