RT Journal Article
SR Electronic
T1 Hydrogen Sulfide in the Rostral Ventrolateral Medulla Inhibits Sympathetic Vasomotor Tone through ATP-Sensitive K<sup>+</sup> Channels
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 458
OP 465
DO 10.1124/jpet.111.180711
VO 338
IS 2
A1 Qi Guo
A1 Sheng Jin
A1 Xiu-Li Wang
A1 Ru Wang
A1 Lin Xiao
A1 Rui-rong He
A1 Yu-ming Wu
YR 2011
UL http://jpet.aspetjournals.org/content/338/2/458.abstract
AB 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.