FAILURE OF L-NITROARGININE, A NITRIC-OXIDE SYNTHASE INHIBITOR, TO AFFECT HYPOTENSION AND PLASMA-PROTEIN EXTRAVASATION PRODUCED BY TACHYKININ NK-1 RECEPTOR ACTIVATION IN RATS

1 We have assessed the effect of L-nitroarginine (L-NOARG), a nitric o xide (NO) synthase inhibitor, on hypotension and plasma protein extrav asation produced by i.v. administraton of substance P (SP) in urethane -anaesthetized rats. 2 I.v. administered SP (1 nmol kg-1) produced max imal blood pressure lowering effect which was not modified by previous administration of L-NOARG (45.6 mumol kg-1 i.v.). The hypotensive res ponse to SP was greatly reduced by the non-peptide SP antagonist, RP 6 7,580 (0.68 mumol kg-1) indicating the involvement of tachykinin NK-1 receptor. L-NOARG caused by itself a sustained increase in both systol ic and diastolic blood pressure. while RP 67,580 was without effect. 3 I.v. administration of SP produced plasma protein extravasation in th e trachea, ureter and urinary bladder (determined by the Evans blue le akage technique). A dose of 10 nmol kg-1 SP was necessary to produce a maximal effect, while the tachykinin NK-1 receptor selective agonist [Sar9]SP sulphone produced a similar maximal response at 3 nmol kg-1 i n the various organs tested. 4 L-NOARG failed to affect plasma protein extravasation produced by either SP or [Sar9]SP sulphone while RP 67, 580 inhibited the response to both agents. 5 The present findings fail to reveal a significant contribution of NO production in the hypotens ive and inflammatory response to NK-1 receptor stimulation in urethane -anaesthetized rats.