title: Pharmacological evidence that NaHS inhibits the vasopressor responses induced by stimulation of the preganglionic sympathetic outflow in pithed rats.
abstract: It has been reported that i.v. administration of NaHS, a donor of H2S, elicited dose-dependent hypotension although the mechanisms are not completely understood. In this regard, several mechanisms could be involved including the inhibition of the vasopressor sympathetic outflow. Thus, this study was designed to determine the potential capability of NaHS to mediate inhibition of the vasopressor responses induced by preganglionic sympathetic stimulation. For this purpose, Wistar rats were anaesthetised, pithed and cannulated for drug administration. In animals pre-treated with gallamine, the effect of i.v. infusion of NaHS (310 and 560μg/kgmin) or its vehicle (phosphate buffer) was determined on the vasopressor responses induced by: (1) sympathetic stimulation (0.03-10Hz); (2) i.v. bolus injections of exogenous noradrenaline (0.03-3μg/kg); or (3) methoxamine (1-100μg/kg). The vasopressor responses induced by preganglionic sympathetic stimulation were dose-dependently inhibited by i.v. infusion of NaHS (310 and 560μg/kgmin), but not by vehicle, particularly at high frequencies. In marked contrast, the vasopressor responses to exogenous noradrenaline or methoxamine were not inhibited by the above doses of NaHS or its vehicle. The above results, taken together, demonstrate that NaHS inhibited the vasopressor responses induced by preganglionic sympathetic outflow by a prejunctional mechanism. This is the first evidence demonstrating this effect by NaHS that may contribute, at least in part, to the hypotension induced by NaHS.
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Del. Tlalpan, C.P. 14330, México D.F., Mexico. Electronic address: dcenturi@cinvestav.mx.
authors.forename: David
authors.initials: D
authors.lastname: Centurión
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Del. Tlalpan, C.P. 14330, México D.F., Mexico.
authors.forename: Saúl Huerta
authors.initials: SH
authors.lastname: De la Cruz
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Del. Tlalpan, C.P. 14330, México D.F., Mexico.
authors.forename: Erika J
authors.initials: EJ
authors.lastname: Gutiérrez-Lara
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Del. Tlalpan, C.P. 14330, México D.F., Mexico.
authors.forename: Jesús H
authors.initials: JH
authors.lastname: Beltrán-Ornelas
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Del. Tlalpan, C.P. 14330, México D.F., Mexico.
authors.forename: Araceli
authors.initials: A
authors.lastname: Sánchez-López
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005725:Ganglia, Autonomic / Q000187:drug effects* / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008729:Methoxamine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology
chemical_list: D013440:Sulfides; D014662:Vasoconstrictor Agents; C025451:sodium bisulfide; D008729:Methoxamine; D009638:Norepinephrine
keywords: Blood pressure; Cardiovascular; H(2)S; Hypotension; Sympathetic outflow