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

Abstract

transfer of cystathionine ␤-synthase into RVLM increases hydrogen sulfide-mediated suppression of sympathetic outflow via KATP channel in normotensive rats. Am J Physiol Heart Circ Physiol 308: H603-H611, 2015. First published January 16, 2015; doi:10.1152/ajpheart.00693.2014.-Hydrogen sulfide has been shown to have a sympathoinhibitory effect in the rostral ventrolateral medulla (RVLM). The present study examined the function of cystathionine ␤-synthase (CBS)/hydrogen sulfide system in the RVLM, which plays a crucial role in the control of blood pressure and sympathetic nerve activity. Adenovirus vectors encoding CBS (Ad-CBS) or enhanced green fluorescent protein (AdEGFP) were transfected into the RVLM in normotensive rats. Identical microinjection of AdCBS into the RVLM had no effect on systolic blood pressure and heart rate (HR) in conscious rats. Acute experiments were performed at day 7 after gene transfer in anesthetized rats. Microinjection of the CBS inhibitors hydroxylamine (HA) or amino-oxyacetate into the RVLM produced an increase in the renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), and HR. There was a potentiation of the increases in RSNA, MAP, and HR because of the CBS inhibitors in AdCBS-injected rats compared with Ad-EGFP-injected rats. Pretreatment with pinacidil, a ATP-sensitive potassium (K ATP) channel activator, abolished the effects of HA in two groups. Microinjection of glibenclamide, a K ATP channel blocker, produced increases in RSNA, MAP, and HR in AdCBS-injected rats. No changes in behavior were observed in AdEGFP-injected rats. Furthermore, Western blot analysis indicated an increase in the expression of sulfonylurea receptor 2 and inward rectifier K ϩ 6.1 in AdCBS-injected rats. These results suggest that the increase in K ATP channels in the RVLM may be responsible for the greater sympathetic outflow and pressor effect of HA in AdCBS-injected rats compared with AdEGFP-injected rats.cystathionine ␤-synthase; rostral ventrolateral medulla; renal sympathetic nerve activity; gene transfer; blood pressure HYDROGEN SULFIDE (H 2 S) is an endothelium-derived hyperpolarizing factor that enhances relaxation of the peripheral vasculature (2, 28). Recent studies (9, 13, 34) have also reported its physiological functions in the central nervous system. In mammalian tissues, H 2 S is produced through degradation of L-cysteine mainly by two main enzymes: cystathionine ␤-synthase (CBS) and cystathionine ␥-lyase (15). CBS is primarily found in the brain, whereas CSE is mainly expressed in the peripheral tissues (15). CBS has been found in regions of the brain, such as the paraventricular nucleus (11) and rostral ventrolateral medulla (RVLM) (13), which are responsible for the regulation of sympathetic nerve activity and thus arterial blood pressure.However, conflicting results have also been reported regarding the role of H 2 S in regulating sympathetic nerve activity and blood pressure. Previous experiments have demonstrated that bilateral microinjection of sodium hydrosulfid...

Role of central hydrogen sulfide on ventilatory and cardiovascular responses to hypoxia in spontaneous hypertensive rats

“…One way or the other, these depolarizing effects seem to be followed by longer latency hyperpolarizations that results from the activation of KATP channels, that have been suggested to be involved not only in the blood pressure regulation (Foster and Coetzee, 2016) but also in pulmonary ventilation, i.e., systems controlled by the NTS. Another putative region potentially affected by AOA is the rostral ventrolateral medulla (RVLM) where an increased KATP channels activity has been suggested to be responsible for a greater sympathetic outflow and pressor effect (Duan et al, 2015). We speculate that the fairly different (accentuated) effects of H2S on respiration and cardiovascular function during hypoxia in SHR may result from the activation of KATP channels in structures of the brain stem by H2S.…”

Critical Role of the Interaction Gut Microbiota – Sympathetic Nervous System in the Regulation of Blood Pressure

“…Furthermore, we found in the W-S group a depletion of Peptococcaceae , a sulfate-reducing bacteria considered to be beneficial in the regulation of BP (Ahmad et al, 2012; Yu et al, 2018). Sulfate-reducing bacteria, and hydrogen sulfide released in the colon may also contribute to the control of arterial BP, being antihypertensive, at least in part, through suppression of sympathetic outflow (Duan et al, 2015). The genus Blautia , which is the main bacterial group in Clostridium coccoides-group, was also found to decrease in Japanese patients with type 2 diabetes, as compared with control subjects (Sato et al, 2014).…”

Hydrogen Sulfide Facilitates the Impaired Sensitivity of Carotid Sinus Baroreflex in Rats with Vascular Calcification

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