title: Hydrogen sulphide-mediated vasodilatation involves the release of neurotransmitters from sensory nerves in pressurized mesenteric small arteries isolated from rats.
abstract: OBJECTIVE
  Hydrogen sulphide (H(2)S) is a gas that has recently been shown to have biological activity. In the majority of blood vessels studied so far, H(2)S has been shown to cause vasorelaxation, although contractile responses have been reported. In the present study, we have made a pharmacological assessment of the effects of H(2)S in mesenteric small arteries isolated from rats.
  
  
  METHODS
  Rat mesenteric small arteries were studied using pressure myography. In pressurised arteries, responses were obtained to the H(2)S donor, sodium hydrogen sulphide (NaHS), in the absence and presence of the NOS inhibitor L-NAME, raised extracellular potassium, the K(ATP) channel inhibitor glibenclamide, the Cl- channel blockers DIDS, NPPB and A9C, the TRPV1 receptor desensitizing agent, capsaicin, the CGRP antagonist, olcegepant, the TRPV1 channel blocker capsazepine and the TRPA1 channel blocker HC-030031.
  
  
  RESULTS
  NaHS produced a vasodilator response in rat mesenteric small arteries held at 90 mmHg. Responses to NaHS were not reproducible. Neither, glibenclamide nor, L-NAME inhibited responses to NaHS. DIDS abolished vasodilator responses to NaHS, but these were unaffected by the chloride channel blockers, NPPB and A9C. Responses to NaHS were attenuated after capsaicin pre-treatment, by a CGRP receptor antagonist and an inhibitor of TRPA1 channels.
  
  
  CONCLUSIONS
  In small arteries isolated from the rat mesentery, NaHS caused a vasodilatation. This response was not reproducible in vitro, since it was mediated by the release of sensory neurotransmitters in a capsaicin-like action. This release was mediated by a H(2)S-induced activation of TRPA1 channels.
authors.affiliation: Cardiovascular Research Group, School of Biomedical Sciences, University of Nottingham, Nottingham, UK.
authors.forename: Benjamin J O
authors.initials: BJ
authors.lastname: White
authors.forename: Paul A
authors.initials: PA
authors.lastname: Smith
authors.forename: William R
authors.initials: WR
authors.lastname: Dunn
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000294:innervation*; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D009213:Myography; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010525:Peripheral Nerves / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D018377:Neurotransmitter Agents; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; D014662:Vasoconstrictor Agents; D002211:Capsaicin; D006862:Hydrogen Sulfide