Abstract
Hydrogen sulfide (H2S) is now recognized as an important signaling molecule and has been shown to have vasodilator and cardio-protectant effects. More recently it has been suggested that H2S may also act within the brain to reduce blood pressure (BP). In the present study we have demonstrated the presence of the H2S-producing enzyme, cystathionine-β-synthase (CBS) in the rostral ventrolateral medulla (RVLM), and the hypothalamic paraventricular nucleus (PVN), brain regions with key cardiovascular regulatory functions. The cardiovascular role of H2S was investigated by determining the BP, heart rate (HR), and lumbar sympathetic nerve activity (LSNA) responses elicited by a H2S donor sodium hydrogen sulfide (NaHS) or inhibitors of CBS, microinjected into the RVLM and PVN. In anesthetized Wistar Kyoto rats bilateral microinjections of NaHS (0.2–2000 pmol/side) into the RVLM did not significantly affect BP, HR, or LSNA, compared to vehicle. Similarly, when the CBS inhibitors, amino-oxyacetate (AOA; 0.1–1.0 nmol/side) or hydroxylamine (HA; 0.2–2.0 nmol/side), were administered into the RVLM, there were no significant effects on the cardiovascular variables compared to vehicle. Microinjections into the PVN of NaHS, HA, and AOA had no consistent significant effects on BP, HR, or LSNA compared to vehicle. We also investigated the cardiovascular responses to NaHS microinjected into the RVLM and PVN in spontaneously hypertensive rats. Again, there were no significant effects on BP, HR, and LSNA. Together, these results suggest that H2S in the RVLM and PVN does not have a major role in cardiovascular regulation.
Highlights
Hydrogen sulfide (H2S) is better known for its pungent odor and toxic properties than its potential therapeutic actions
The cardiovascular role of H2S was investigated by determining the blood pressure (BP), heart rate (HR), and lumbar sympathetic nerve activity (LSNA) responses elicited by a H2S donor sodium hydrogen sulfide (NaHS) or inhibitors of CBS, microinjected into the rostral ventrolateral medulla (RVLM) and paraventricular nucleus (PVN)
Effect of NaHS microinjected into the RVLM Sodium hydrogen sulfide (0.2–2000 pmol/side) microinjected into the RVLM resulted in small increases in MAP and HR but these were not significantly different from vehicle (Figure 1B)
Summary
Hydrogen sulfide (H2S) is better known for its pungent odor and toxic properties than its potential therapeutic actions. It is becoming increasingly clear, that H2S, like other gaseous transmitters, such as nitric oxide (NO), is an important endogenous signaling molecule in many physiological functions (Abe and Kimura, 1996; Ufnal et al, 2008; Yang et al, 2008; Calvert et al, 2009; Hart, 2011). Hydrogen sulfide has a number of effects including neuromodulation, anti-oxidant, anti-inflammatory, and cardiovascular actions (Kimura, 2002; Mustafa et al, 2009; Gadalla and Snyder, 2010). Recent work using CSE knockout mice has suggested that endogenously produced H2S is necessary for maintaining normal BP since these animals develop hypertension and have an attenuated endothelium-dependent vasorelaxation (Yang et al, 2008)
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