title: The nitric oxide synthesis/pathway mediates the inhibitory serotoninergic responses of the pressor effect elicited by sympathetic stimulation in diabetic pithed rats.
abstract: We investigated the involvement of the nitric oxide pathway in the inhibitory mechanisms of 5-hydroxytryptamine (5-HT) in the pressor responses induced by stimulation of sympathetic vasopressor outflow in diabetic pithed rats. Diabetes was induced in male Wistar rats by a single s.c. injection of alloxan. Four weeks later, the animals were anaesthetized, pretreated with atropine, and pithed. Electrical stimulation of the sympathetic outflow from the spinal cord (0.1, 0.5, 1 and 5 Hz) resulted in frequency-dependent increases in blood pressure. The inhibition of electrically induced pressor responses by 5-HT (10 microg/kg/min) in diabetic pithed rats could not be elicited after i.v. treatment with 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10 microg/kg), a guanylyl cyclase inhibitor, or N-omega-L-Arginine methyl ester hydrochloride (L-NAME) (10 mg/kg), a nitric oxide synthase (NOS) inhibitor. The inhibitory effect produced by infusion of the selective 5-HT(1A) receptor agonist 8-hydroxydipropylaminotretalin hydrobromide (8-OH-DPAT) (20 microg/kg/min) was abolished in the presence of ODQ (10 microg/kg), or L-NAME (10 mg/kg) in diabetic pithed rats. The administration of L-Arginine (100 mg/kg) 30 min after L-NAME reproduced the inhibitory effect caused by 5-HT (10 microg/kg/min) and 8-OH-DPAT (20 microg/kg/min) on the electrically induced pressor responses, whereas in the presence of D-Arginine (100 mg/kg)+L-NAME the 5-HT or 8-OH-DPAT inhibitory effect on the pressor responses was abolished. In conclusion, in diabetic pithed rats, the inhibition produced by prejunctional 5-HT(1A) activation on electrically induced sympathetic pressor responses is mediated by the NO synthesis/pathway.
authors.affiliation: Laboratorio de Farmacognosia y Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno, ES-37007 Salamanca, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: García
authors.forename: Asunción
authors.initials: A
authors.lastname: Morán
authors.forename: María
authors.initials: M
authors.lastname: Luisa Martín
authors.forename: Mariette
authors.initials: M
authors.lastname: Barthelmebs
authors.forename: Luis
authors.initials: L
authors.lastname: San Román
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D014363:Tryptamines / Q000494:pharmacology; D014661:Vasoconstriction
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D010069:Oxadiazoles; D011810:Quinoxalines; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; D044282:Receptor, Serotonin, 5-HT1A; C085632:L 694247; D009569:Nitric Oxide; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D001285:Atropine; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine