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 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 (L-NAME, 200 µM, 50 nl) partially inhibited the sympathoinhibitory effects of NaHS. Prior microinjection of Bay K8644 (1 µM, 50 nl), an agonist of Ca2+ channels, did not alter the effects of NaHS. Infusion of hydroxylamine (HA, 30 mM, 50 nl), a cystathionine β-synthase (CBS) inhibitor, increased BP, 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.
- Received February 25, 2011.
- Revision received May 4, 2011.
- Accepted May 4, 2011.
- The American Society for Pharmacology and Experimental Therapeutics