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 oxide (NO) synthase inhibitor, on hypotension and plasma protein extravasation produced by i.v. administration of substance P (SP) in urethane-anaesthetized rats. 2. I.v. administered SP (1 nmol kg-1) produced maximal blood pressure lowering effect which was not modified by previous administration of L-NOARG (45.6 mumol kg-1 i.v.). The hypotensive response to SP was greatly reduced by the nonpeptide SP antagonist, RP 67,580 (0.68 mumol kg-1) indicating the involvement of tachykinin NK-1 receptor. L-NOARG caused by itself a sustained increase in both systolic and diastolic blood pressure, while RP 67,580 was without effect. 3. I.v. administration of SP produced plasma protein extravasation in the trachea, ureter and urinary bladder (determined by the Evans blue leakage 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 in 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 hypotensive and inflammatory response to NK-1 receptor stimulation in urethane-anaesthetized rats.
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Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Giuliani
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Maggi
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D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001798:Blood Proteins / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D007275:Injections, Intravenous; D054833:Isoindoles; D008297:Male; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D051381:Rats; D017208:Rats, Wistar; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D013373:Substance P / Q000037:antagonists & inhibitors / Q000502:physiology*
D001798:Blood Proteins; D007211:Indoles; D054833:Isoindoles; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D019335:Nitroarginine; D013373:Substance P; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases