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

Involvement of endogenous central hydrogen sulfide (H2S) in hypoxia-induced hypothermia in spontaneously hypertensive rats

“…During basal conditions (normoxia) we observed normal heart rate and elevated arterial pressure in SHR (see Supplementary material) as traditionally reported (Campos et al 2014;Okamoto and Aoki 1963;Totola et al 2013). The role of endogenous H 2 S in modulating hypoxia-induced adjustments in arterial blood pressure and pulmonary ventilation in SHR has been recently assessed by Sabino and colleagues, showing that endogenous H 2 S plays important modulatory roles in ventilatory and cardiovascular responses to hypoxia in SHR, inhibiting the cardiovascular responses and stimulating the respiratory system (Sabino et al 2016). During the control period (normoxia) Tb of SHR was similar to that of Wistar rats, being in agreement D r a f t with some previous reports (Campos et al 2014;Morley et al 1990) and opposite to other ones (Collins et al 1987;O'Donnel and Volicer 1981).…”

“…However, it is not known whether this gasomodulator plays a role in the thermoregulatory system of spontaneously hypertensive rats (SHR) whose sensitivity to hypoxia is increased (Peng et al 2014) and the autonomic functions and consequently Tb adjustments are abnormal (Campos et al 2014;Collins et al 1987;Hajós and Engberg 1986;Morley et al 1990;O'Donnell and Volicer 1981). Of particular interest to the present report is that endogenous H 2 S in the caudal brainstem of SHR regulates ventilatory and D r a f t cardiovascular responses to hypoxia (Sabino et al 2016). Nevertheless, no information is available as to the putative role of H 2 S in modulating hypothermic response to hypoxia in SHR, although we know that SHR Tb adjustments are peculiar (Campos et al 2014;Collins et al 1987;Hajós and Engberg 1986;Morley et al 1990;O'Donnell and Volicer 1981) like those seen in hypertensive humans (Kenney 1985;.…”

Excitatory Modulation of the preBötzinger Complex Inspiratory Rhythm Generating Network by Endogenous Hydrogen Sulfide

“…Another important consideration is that chemosensory feedback loops were opened in our studies via muscle paralysis and mechanical ventilation so that AOAA-induced changes in ventilatory drive would not affect blood gases. Intact feedback control loops in previous experiments (da Silva et al, 2014; Kwiatkoski et al, 2014; Sabino et al, 2016) could obscure basal modulation by H 2 S because AOAA would reduce H 2 S levels, causing a reduction in ventilation, increased CO 2 , reduced O 2 and a compensatory increase in ventilation.…”

“…Under in vitro conditions, inhibition of CBS activity with AOAA or hydroxylamine (NH 2 OH) reduced basal frequency in 700 (Figure 2) and 1,200 μm thick slices (Hu et al, 2008), but had no effect in 800–900 μm thick slices (Pan et al, 2011). Local injection of AOAA into the preBötC in vivo reduced frequency in anesthetized, paralyzed rats (Figure 4), but intraventricular delivery of AOAA in vivo did not affect basal respiratory activity in unanaesthetized rats (da Silva et al, 2014; Kwiatkoski et al, 2014; Sabino et al, 2016). Variable effects in vitro are difficult to reconcile but could reflect differences in slice architecture or efficacy of the enzyme inhibitor.…”

“…Inhibitory actions of H 2 S in other parts of the respiratory network have not been directly demonstrated in hypoxia but it is likely since H 2 S actions vary in other parts of the brain and also between normoxia, hypoxia and hypercapnia. For example, in hypothalamus of adult unanaesthetized rats, endogenous production of H 2 S attenuates the hypoxic ventilatory response (Kwiatkoski et al, 2014), while in unrestrained, spontaneously hypertensive rats, endogenous H 2 S acts centrally to enhance the ventilatory response to hypoxia (Sabino et al, 2016). It also acts in the brainstem to enhance the ventilatory response of adult Wistar rats to hypercapnia (da Silva et al, 2014).…”