TRPA1, but not TRPV1, is involved in the increase of the non-adrenergic non-cholinergic outflow induced by hydrogen sulfide in pithed rats.

Hydrogen sulfide (H2S) is a gasotransmitter that modulates the peripheral transmission regulating the vascular tone. In vitro studies have suggested that H2S induces vasodilation by stimulating capsaicin-sensitive sensory neurons. This study was designed to determine the effects of H2S on the non-adrenergic/non-cholinergic (NANC) outflow in the pithed rat, and the underlying mechanisms. For that purpose, 72 male Wistar rats were anesthetized, pithed and the carotid, femoral and jugular veins were cannulated and then divided into two main sets. The first set of animals (n = 48) was used to determine the effect of NaHS (H2S donor) on the vasodepressor responses induced by: 1) NANC outflow electrical stimulation (n = 24); and 2) i.v. bolus of α-CGRP (n = 24) and subdivided into 4 groups (n = 6 each): 1) control group (without infusion); continuous infusion of: 2) PBS (vehicle; 0.02 ml/kg·min); 3) NaHS 10 μg/kg·min; and 4) NaHS 18 μg/kg·min. The second set of animals (n = 24) received an i.v. bolus of either (1) HC 030031 (TRPA1 channel antagonist; 18 μg/kg; n = 12) or (2) capsazepine (TRPV1 channel antagonist; 100 μg/kg; n = 12) in presence and absence of 18 µg/kg·min NaHS i.v. continuous infusion to determine the underlying mechanism of the NaHS effect on the NANC outflow. Our results show that NaHS infusion increased the vasodepressor responses induced by electrical stimulation, but not by α-CGRP, effect that was abolished by HC030031 and remained unaffected after capsazepine. These data suggest that activation of TRPA1 channels, but no TRPV1, is responsible for the NaHS-induced NANC neurotransmission stimulation.