Cardiovascular pharmacology Pharmacological evidence that NaHS inhibits the vasopressor responses induced by stimulation of the preganglionic sympathetic outflow in pithed rats David Centurión n , Saúl Huerta De la Cruz, Erika J. Gutiérrez-Lara, Jesús H. Beltrán-Ornelas, Araceli Sánchez-López Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Del. Tlalpan, C.P.14330, México D.F., Mexico article info Article history: Received 17 August 2015 Received in revised form 25 November 2015 Accepted 27 November 2015 Available online 28 November 2015 Keywords: Blood pressure Cardiovascular Hypotension H 2 S Sympathetic outflow abstract It has been reported that i.v. administration of NaHS, a donor of H 2 S, 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 560 μg/ kg min) or its vehicle (phosphate buffer) was determined on the vasopressor responses induced by: (1) sym- pathetic stimulation (0.03–10 Hz); (2) i.v. bolus injections of exogenous noradrenaline (0.03–3 μg/kg); or (3) methoxamine (1–100 μg/kg). The vasopressor responses induced by preganglionic sympathetic stimulation were dose-dependently inhibited by i.v. infusion of NaHS (310 and 560 μg/kg min), but not by vehicle, parti- cularly 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. & 2015 Elsevier B.V. All rights reserved. 1. Introduction H 2 S is a gasotransmitter that mediates complex responses in the cardiovascular system such as cardioprotection and vasculo- protection (Wang, 2012). In isolated blood vessels, H 2 S produces relaxation mainly by activation of K ATP channels (Tang et al., 2010) while in anaesthetised rats NaHS, a donor of H 2 S, mediates hy- potension (Ali et al., 2006) although the mechanisms are more complex and several unidentified mechanisms could be involved. Indeed, in anaesthetised rats, hypotension to NaHS is not mediated by nitric oxide release, K þ channels, BKCa channels, cGMP, release of arachidonic acid metabolites or p450 epoxygenase metabolites. This effect was not mediated by adrenergic or cholinergic system since the hypotension to NaHS was unaffected by atropine, phentholamine or hexamethonium (Yoo et al., 2015). Thus, the authors concluded that uncertain mechanisms mediate hypoten- sion to NaHS in anaesthetised rats. One of the mechanisms that we explore in this study is the capability of NaHS to inhibit the vascular sympathetic outflow. In this context, it has been previously shown that NaHS inhibited [H 3 ]-noradrenaline release elicited by electrically field stimulation in the sympathetic porcine iris-ciliary bodies (Kulkarni et al., 2009). The enzyme inhibitors propargylglycine (CSE) and ami- nooxyacetic acid (CBS) blocked this effect suggesting that this ef- fect was dependent on intramural biosynthesis of H 2 S. On this basis, the present study was designed to determine the potential capability of NaHS to inhibit the vasopressor sympathetic outflow in pithed rats. This mechanism may be involved in the vasodepressor effect induced by NaHS. 2. Materials and methods 2.1. Animals Male Wistar normotensive rats (270–300 g) were housed in plastic cages in a special temperature-controlled room (22 72 °C, 50% humidity) on a 12/12-h light-dark cycle (with light beginning at 7:00 a.m.), with food and water freely available in their home Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/ejphar European Journal of Pharmacology http://dx.doi.org/10.1016/j.ejphar.2015.11.057 0014-2999/& 2015 Elsevier B.V. All rights reserved. n Corresponding author. E-mail address: dcenturi@cinvestav.mx (D. Centurión). URL: http://farmacobiologia.cinvestav.mx/PersonalAcad%C3%A9mico/ DrDavidCenturi%C3%B3nPacheco.aspx (D. Centurión). European Journal of Pharmacology 770 (2016) 40–45