Pharmacological evidence that potassium channels mediate hydrogen sulfide-induced inhibition of the vasopressor sympathetic outflow in pithed rats

Abstract

Hydrogen sulfide (H₂S) is a gasotransmitter that modulates neurotransmission. Indeed, it has been recently demonstrated that H₂S inhibits the sympathetic outflow in male rats, although the mechanisms remain elusive. Thus, this study evaluated the role of potassium channels on NaHS-induced sympathoinhibition. For this purpose, male and female Wistar rats were anesthetized, pithed, and cannulated. After that, animals received selective electrical stimulation of the vasopressor sympathetic outflow (T₇-T₉). Prior to 310 μg/kg·min NaHS i.v. continuous infusion animals received: (1) bidistilled water (tetraethylammonium, TEA; 4-aminopyridine, 4-AP; and barium chloride, BaCl₂; vehicle; 1 ml/kg); (2) TEA (non-selective K⁺ channels blocker; 16.5 mg/kg); (3) 4-AP (non-selective voltage-dependent K⁺ channels blocker; 5 mg/kg); (4) BaCl₂ (inward rectifier K⁺ channels blocker; 65 μg/kg); (5) DMF 5%, glucose 10% and NaOH 0.1 N (glibenclamide vehicle; 1 ml/kg); (6) glibenclamide (ATP-dependent K⁺ channels blocker; 10 mg/kg); (7) DMSO 4% (paxilline vehicle; 1 ml/kg); and (8) paxilline (large-conductance voltage- and Ca²⁺-activated K⁺ channel blocker; 90 μg/kg). The NaHS-induced sympathoinhibition was: (1) equally observed in male and female rats; (2) unaffected by vehicles; (3) reversed by the potassium channel blockers. Taken together, our results suggest that NaHS-induced sympathoinhibition does not depend on sex and it is mediated by the activation of several potassium channels.

Keywords: Blood pressure; Hydrogen sulfide; Potassium channels; Sympathetic outflow.