Abstract
Hydrogen sulfide (H2S) acts as an endogenous gaseous transmitter in the central nervous system and plays important roles in regulating cardiovascular function. The rostral ventrolateral medulla (RVLM) is a putative critical central region in the control of sympathetic vasomotor tone and plays an important role in the baroreflex by integrating the inputs from a variety of visceral and somatic stimuli. In this study, we tested the hypothesis that H2S decreases sympathetic vasomotor tone through ATP-sensitive potassium channels (KATP) in the RVLM. The arterial blood pressure (ABP), heart rate (HR), and renal sympathetic nerve activity (RSNA) of anesthetized rats were recorded. Bilateral microinjections of sodium hydrosulfide (NaHS; 4, 8, and 16 mM, 50 nl), an H2S donor, into the RVLM decreased ABP, HR, and RSNA in a dose-dependent manner. Preinjection of glibenclamide (40 μM, 50 nl), a KATP channel blocker, abolished the sympathoinhibitory effects of NaHS (8 mM, 50 nl). Preinjection of a nitric-oxide synthase inhibitor, Nω-nitro-l-arginine methyl ester (200 μM, 50 nl) partially inhibited the sympathoinhibitory effects of NaHS. Prior microinjection of 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-[trifluoromethyl]phenyl)pyridine-3-carboxylic acid methyl ester (Bay K8644) (1 μM, 50 nl), an agonist of Ca2+ channels, did not alter the effects of NaHS. Infusion of hydroxylamine (30 mM, 50 nl), a cystathionine β-synthase inhibitor, increased ABP, HR, and RSNA. Taken together, these findings suggest that exogenous H2S in the RVLM inhibits sympathetic vasomotor tone by opening KATP channels. Nitric-oxide signaling may partially be involved in the sympathoinhibitory effect of H2S in the RVLM.
Footnotes
This work was supported by the Program for New Century Excellent Talents in University from the Education Ministry of China [Grant NCET-07-0252], the National Natural Science Foundation of China [Grant 30772082], Hebei Province Funds for Distinguished Young Scientists [Grant 2010000471], and the Natural Science Foundation of Hebei Province of China [Grants C2007000821, C2008000931].
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
doi:10.1124/jpet.111.180711.
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ABBREVIATIONS:
- H2S
- hydrogen sulfide
- NO
- nitric oxide
- NOS
- NO synthase
- KATP
- ATP-sensitive potassium channel
- CBS
- cystathionine β-synthase
- CSE
- cystathionine γ-lyase
- DMSO
- dimethyl sulfoxide
- l-NAME
- Nω-nitro-l-arginine methyl ester
- NaHS
- sodium hydrogen sulfide
- RVLM
- rostral ventrolateral medulla
- ABP
- arterial blood pressure
- HR
- heart rate
- RSNA
- renal sympathetic nerve activity
- HA
- hydroxylamine
- Bay K8644
- 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-[trifluoromethyl]phenyl)pyridine-3-carboxylic acid methyl ester
- PBS
- phosphate-buffered saline
- GABA
- γ-aminobutyric acid.
- Received February 25, 2011.
- Accepted May 4, 2011.
- Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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