Hydrogen sulfide (H 2 S), traditionally known for its smell and toxicity, is now increasingly recognised as a gasotransmitter. It is produced endogenously by several enzymes and has biological effects, including neuromodulation, cardiovascular and antioxidant effects. In the peripheral cardiovascular system, H 2 S causes vasodilation and systemic administration of a H 2 S donor, sodium hydrogen sulfide (NaHS), reduces blood pressure in a dose dependent manner. The rostral ventrolateral medulla (RVLM) and the hypothalamic paraventricular nucleus (PVN) are brain nuclei with demonstrated involvement in increased sympathetic nerve activity observed in cardiovascular pathologies. The aim of this study was to investigate the possible role of H 2 S as a central cardiovascular regulator via the RVLM and PVN.. The presence of the H 2 S-producing enzyme, cystathionine β synthase (CBS) in the RVLM and PVN was demonstrated by western blotting and immunohistochemistry. Nerve recording studies were performed on anaesthetised male Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). Bilateral microinjections of NaHS (0.2 – 2000 pmol/side), or inhibitors of CBS (hydroxylamine, HA, 0.2 – 2.0 nmol/side; or amino-oxyacetate, AOA, 0.1 – 1.0 nmol/side) into the RVLM did not significantly affect blood pressure (BP), heart rate (HR) or lumbar sympathetic nerve activity (LSNA), compared to vehicle in WKY rats. Microinjections into the PVN of NaHS, HA and AOA had no consistent significant effects on BP, HR or LSNA compared to vehicle in WKY rats. NaHS microinjected into the PVN or RVLM of SHR rats did not significantly affect BP, HR or LSNA compared to vehicle. Together, these results suggest that H 2 S may not have a major cardiovascular regulatory role in the RVLM and PVN. H 2 S is produced in peripheral blood vessels via the enzyme cystathionine-γ-lyase (CSE). It is thought to be an important endogenous vasoactive mediator, since CSE gene deletion results in increased blood pressure. The aim of this study was to examine the mechanism of H 2 S-induced vasodilation of cerebral arteries. Vasorelaxation responses in middle cerebral arteries (MCA) from male Sprague-Dawley rats were examined using wire myography. Inhibiting K + conductance with KCl (50mM) significantly attenuated NaHS-induced relaxation, increasing the EC 50 by 4 fold. 4,4-diisothiocyanatostilbene-2,2-disulfonic acid (DIDS, 300µM) caused a significant 10-fold rightward shift of the NaHS concentration-response curve. Nifedipine (3µM), a blocker of L-type calcium channels, significantly reduced the maximum relaxation elicited by NaHS by 30%. These findings suggest that H 2 S mediated relaxation of MCA is DIDS sensitive and partly mediated by inhibition of L-type calcium channels with an additional contribution by potassium channels. H 2 S has antioxidant effects which may protect against endothelial dysfunction. The aim of this study was to examine the effect of streptozotocin-induced diabetes on the MCA response to H 2 S.. Diabetic MCA exhibited endothelial dysfunction, however, their response to NaHS was unaltered. L-cysteine-induced relaxation was enhanced in diabetic MCA. The lucigenin assay demonstrated increased superoxide generation from both aorta and cerebral vessels of diabetic animals. NaHS decreased superoxide generation from diabetic, but not control MCA. The results suggest that production of H2S is increased in diabetic MCA and H 2 S appears to act as an antioxidant in these vessels in vitro
