부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ejphar.2006.03.020 Byline: Monica Garcia (a), Asuncion Moran (a), Maria Luisa Martin (a), Mariette Barthelmebs (b), Luis San Roman (a) Keywords: 5-hydroxytryptamine; Nitric oxide; Experimental diabetes; 5-HT.sub.1A receptors; Prejunctional inhibition 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 [mu]g/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 [mu]g/kg), a guanylyl cyclase inhibitor, or N-I-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.sub.1A receptor agonist 8-hydroxydipropylaminotretalin hydrobromide (8-OH-DPAT) (20 [mu]g/kg/min) was abolished in the presence of ODQ (10 [mu]g/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 [mu]g/kg/min) and 8-OH-DPAT (20 [mu]g/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.sub.1A activation on electrically induced sympathetic pressor responses is mediated by the NO synthesis/pathway. Author Affiliation: (a) Laboratorio de Farmacognosia y Farmacologia, Departamento de Fisiologia y Farmacologia, Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno, ES-37007 Salamanca, Spain (b) Laboratoire de Physiologie et Pharmacologie Renovasculaires (U727 INSERM), Faculte de Medecine, Universite Louis Pasteur, F67085 Strasbourg Cedex, France Article History: Received 3 November 2005; Revised 2 March 2006; Accepted 13 March 2006