INVOLVEMENT OF NITRIC-OXIDE IN THE SMOOTH-MUSCLE TONE OF THE ISOLATEDCANINE 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 pr essure (SAPP) and spleen weight were recorded continuously. An augment ed smooth muscle tone was maintained by a continuous intra-arterial in fusion of noradrenaline (0.01-0.1 mu mol min(-1)) throughout the exper iment. 2 Intra-arterial infusion of indomethacin (5.6 mu M) significan tly elevated (P < 0.05) the augmented vascular tone and the subsequent infusion of L-NAME (10 mu M) further raised this vascular tone signif icantly (P < 0.01), 3 The splenic vasoconstrictor response to L-NAME w as significantly (P < 0.05) reduced by the subsequent infusion of L-ar ginine (300 mu M) but not of D-arginine (300 mu M). 4 Neither L-NAME n or D-NAME had any effect on the basal vascular tone or the spleen weig ht in conditions of either basal or augmented tone. 5 Bolus injection of acetylcholine, substance P, sodium nitroprusside and isoprenaline c aused short-lasting reductions in the SAPP. 6 The splenic vasodilator responses to ACh and SP, but not those to SNP and ISO, were significan tly (P < 0.05) reduced by the infusion of L-NAME (10 mu M), methylene blue (30 mu M) but not of D-NAME (10 mu M). 7 The reductions in the va sodilator responses to ACh and SP caused by L-NAME were partially reve rsed by L-arginine (300 mu M), but not by D-arginine (300 mu M). 8 The results demonstrate the contribution of nitric oxide (NO) release to the maintenance of the augmented splenic vascular tone and also the co ntribution of NO to the splenic vasodilator responses to ACh and SP.