Hydrogen Sulfide in the RVLM and PVN has No Effect on Cardiovascular Regulation

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.

Gene transfer of cystathionine β-synthase into RVLM increases hydrogen sulfide-mediated suppression of sympathetic outflow via KATP channel in normotensive rats

“…Contradictory results have been reported by several studies concerning the role of H 2 S in the regulation of cardiovascular function in the RVLM (13,26). These inconsistent results are most likely caused by the instability of the H 2 S donor.…”

“…Previous experiments have demonstrated that bilateral microinjection of sodium hydrosulfide (NaHS), an H 2 S donor, into the RVLM decreases arterial blood pressure, and the CBS inhibitor hydroxylamine (HA) produces a pressor response (13). Contrary, another study has shown that the microinjection of NaHS into the RVLM has no effect on mean arterial pressure (MAP) (26). Furthermore, conflicting results have been obtained with respect to the effects of H 2 S in the paraventricular nucleus (11,26).…”

“…Contrary, another study has shown that the microinjection of NaHS into the RVLM has no effect on mean arterial pressure (MAP) (26). Furthermore, conflicting results have been obtained with respect to the effects of H 2 S in the paraventricular nucleus (11,26). Although the effect of H 2 S or CBS inhibitors in the RVLM on cardiovascular function has been extensively investigated, most studies are conducted in acute experimental conditions and with the use of anesthetized animals.…”

Pharmacological evidence that NaHS inhibits the vasopressor responses induced by stimulation of the preganglionic sympathetic outflow in pithed rats

“…However, the role of NaHS in regulating blood pressure in the central nervous system (CNS) is still controversial since microinjection of NaHS in RVLM had no significant effect on blood pressure or heart rate (Streeter et al, 2011). Any way, we can exclude a CNS effect of NaHS since the CNS was destroyed in pithed rat.…”

“…In isolated blood vessels, H 2 S produces relaxation mainly by activation of K ATP channels (Tang et al, 2010) while in anaesthetised rats NaHS, a donor of H 2 S, mediates hypotension (Ali et al, 2006) although the mechanisms are more complex and several unidentified mechanisms could be involved. Indeed, in anaesthetised rats, hypotension to NaHS is not mediated by nitric oxide release, Kþ channels, BKCa channels, cGMP, release of arachidonic acid metabolites or p450 epoxygenase metabolites.…”