OP24 Characterization of TRPA1-mediated and TRPA1-independent microcirculatory responses to hydrogen sulfide in mice

Abstract

Capsaicin-sensitive sensory neurons express several ion channels of the TRP family, such as transient receptor potential ankyrin 1 (TRPA1) receptors. TRPA1 can be activated by several chemical stimuli, such as allylisothiocyanate (AITC) or cinnamaldehyde resulting in the release of inflammatory neuropeptides, e.g. calcitonin gene-related peptide (CGRP) [1] . Recently, the gaseous mediator hydrogen sulfide (H2S) was suggested to have effect on capsaicin-sensitive sensory neurons acting via TRPA1 receptors. Microcirculatory changes in the mouse ear and hind paw have been investigated in this study. Balb/c, C57BL/6, TRPA1 KO and TRPV1 KO mice (20–30 g) were treated with sodium hydrogen sulfide (NaHS) or AITC. Ipsilateral ears of the animals were treated with 2% AITC or 5% NaHS. Contralateral ears received respective vehicles. Balb/c mice received selective TRPA1 receptor antagonist HC-030031 (i.p., 30 or 100 mg/kg). NaHS (0.5 μmol/10 μL Tyrode) was injected s.c. into hind paws of C57BL/6 and TRPA1 KO mice. Skin blood flow was detected by laser Doppler imaging. AITC treatment of mouse ears led to 29.8 ± 2.8% increase in blood flow. NaHS elevated cutaneous blood flow of the mouse ears by 61 ± 4.5%. Effect of NaHS on microcirculation was ameliorated by HC-030031. Blood flow of TRPA1 KO mice showed significantly smaller increase in response to NaHS compared to the wild-type counterparts. Vasodilatation in TRPV1 KO animals did not differ from control. CGRP8−37 peptide antagonist of CGRP only partly inhibited the response. Intraplantar administration of NaHS elevated blood flow of murine hind paws by 34.1 ± 2.8%. The plantar microcirculatory response to NaHS was unaffected by genetic lack of TRPA1 receptor or resiniferatoxin pretreatment. We conclude that NaHS-induced vasodilatation in the mouse ear is partly mediated by TRPA1 receptors, but is independent of sensory nerves in the skin of the hind paw.