title: Hydrogen sulfide regulates cardiovascular function by influencing the excitability of subfornical organ neurons.
abstract: Hydrogen sulfide (H2S), a gasotransmitter endogenously found in the central nervous system, has recently been suggested to act as a signalling molecule in the brain having beneficial effects on cardiovascular function. This study was thus undertaken to investigate the effect of NaHS (an H2S donor) in the subfornical organ (SFO), a central nervous system site important to blood pressure regulation. We used male Sprague-Dawley rats for both in vivo and in vitro experiments. We first used RT-PCR to confirm our previous microarray analyses showing that mRNAs for the enzymes required to produce H2S are expressed in the SFO. We then used microinjection techniques to investigate the physiological effects of NaHS in SFO, and found that NaHS microinjection (5 nmol) significantly increased blood pressure (mean AUC = 853.5±105.7 mmHg*s, n = 5). Further, we used patch-clamp electrophysiology and found that 97.8% (88 of 90) of neurons depolarized in response to NaHS. This response was found to be concentration dependent with an EC50 of 35.6 µM. Coupled with the depolarized membrane potential, we observed an overall increase in neuronal excitability using an analysis of rheobase and action potential firing patterns. This study has provided the first evidence of NaHS and thus H2S actions and their cellular correlates in SFO, implicating this brain area as a site where H2S may act to control blood pressure.
authors.affiliation: Queen's University, Department of Biomedical and Molecular Sciences, Kingston, Ontario, Canada.
authors.forename: Markus
authors.initials: M
authors.lastname: Kuksis
authors.affiliation: Queen's University, Department of Biomedical and Molecular Sciences, Kingston, Ontario, Canada.
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Smith
authors.affiliation: Queen's University, Department of Biomedical and Molecular Sciences, Kingston, Ontario, Canada.
authors.forename: Alastair V
authors.initials: AV
authors.lastname: Ferguson
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D064426:Gasotransmitters / Q000378:metabolism / Q000494:pharmacology*; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013356:Subfornical Organ / Q000378:metabolism*
chemical_list: D064426:Gasotransmitters; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D006862:Hydrogen Sulfide