title: The cyclooxygenase and nitric oxide synthesis/pathways mediate the inhibitory serotonergic response to the pressor effect elicited by sympathetic stimulation in long-term diabetic pithed rats.
abstract: We investigated the mechanisms involved in the 5-hydroxytriptaminergic inhibitory action on the pressor responses elicited by sympathostimulation in long-term-diabetic pithed rats. Diabetes was induced in rats by alloxan administration. Eight weeks later, the animals were anaesthetized and pithed. The action and mechanisms of 5-HT were analysed based on the pressor responses induced by sympathostimulation. In 8-week-diabetic animals, 5-HT (20 µg/kg/min) inhibits the pressor effect of sympathostimulation which is reproduced by two selective 5-HT(1A) and 5-HT(2) receptor agonists: 8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT, 5 µg/kg/min) and α-methyl-5-HT (5 µg/kg/min). A bolus injection of 1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin-1-one (ODQ, 10 µg/kg), or L-arginine HCl, N(ω)-L-arginine methyl ester hydrochloride (L-NAME, 10 mg/kg), an inhibitor of NO production, prior to the infusion of 8-OH-DPAT (5 µg/kg/min) reversed the inhibitory effect of 8-OH-DPAT. The inhibitory effect of infusion of α-methyl 5-HT (5 µg/kg/min) was abolished in the presence of indomethacin (2 mg/kg), a non-selective cyclooxygenase (COX) inhibitor, or FR 122047 (1.5 mg/kg) or nimesulide (1.5 mg/kg), two selective COX-1 and COX-2 inhibitors, respectively, in long-term-diabetic pithed rats. Our results indicate that 5-HT inhibition of the pressor responses induced by electrical stimulation is mediated both by the NO and COX pathways in long-term-diabetic rats.
authors.affiliation: Departamento de Fisiología y Farmacología, Laboratorio de Farmacología, Facultad de Farmacia, Universidad de Salamanca, Salamanca, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Restrepo
authors.forename: M
authors.initials: M
authors.lastname: García
authors.forename: C
authors.initials: C
authors.lastname: López
authors.forename: M L
authors.initials: ML
authors.lastname: Martín
authors.forename: L
authors.initials: L
authors.lastname: San Román
authors.forename: A
authors.initials: A
authors.lastname: Morán
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000496:Alloxan; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D015398:Signal Transduction; D013564:Sympathetic Nervous System / Q000502:physiology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: C116907:1H-(1,2,4)oxadiazolo(4,3-a)-quiloxalin-1-one; D010069:Oxadiazoles; D010879:Piperazines; D013844:Thiazoles; C085131:1-((4,5-bis(4-methoxyphenyl)-2-thiazoyl)carbonyl)-4-methylpiperazine; C042390:alpha-methylserotonin; D009569:Nitric Oxide; D012701:Serotonin; D000496:Alloxan; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D011451:Prostaglandin-Endoperoxide Synthases; D019331:NG-Nitroarginine Methyl Ester