Hydrogen sulfide in the rostral ventrolateral medulla inhibits sympathetic vasomotor tone through ATP-sensitive K+ channels.

Hydrogen sulfide (H(2)S) 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 H(2)S decreases sympathetic vasomotor tone through ATP-sensitive potassium channels (K(ATP)) 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 H(2)S donor, into the RVLM decreased ABP, HR, and RSNA in a dose-dependent manner. Preinjection of glibenclamide (40 μM, 50 nl), a K(ATP) channel blocker, abolished the sympathoinhibitory effects of NaHS (8 mM, 50 nl). Preinjection of a nitric-oxide synthase inhibitor, N(ω)-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 Ca(2+) 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 H(2)S in the RVLM inhibits sympathetic vasomotor tone by opening K(ATP) channels. Nitric-oxide signaling may partially be involved in the sympathoinhibitory effect of H(2)S in the RVLM.