Involvement of endogenous hydrogen sulfide (H2S) in the rostral ventrolateral medulla (RVLM) in hypoxia-induced hypothermia.

Hypoxia evokes a regulated decrease in deep body temperature (Tb). Hydrogen sulfide (H2S), a signaling molecule that belongs to the gasotransmitter family, has been demonstrated to participate in several brain-mediated responses. Rostral ventrolateral medulla (RVLM) is a brainstem region involved in thermoregulation. Recently, it has been shown that exogenous H2S modulates RVLM activity. In the present study, we investigated whether endogenously produced H2S in the RVLM plays a role in the control of hypoxia-induced hypothermia. Tb was measured before and after bilateral microinjection of aminooxyacetate (AOA, 0.2, 1 and 2 pmol/100 nl, a cystathionine ß-synthase, CBS, inhibitor) or vehicle into the RVLM followed by a 60-min normoxia (21% inspired O2) or hypoxia (7% inspired O2) exposure. Microinjection of AOA or vehicle did not change Tb during normoxia. Exposure to hypoxia evoked a typical decrease in Tb. Microinjection of AOA (2 pmol) into the RVLM followed by hypoxia significantly attenuated the decrease in Tb. Thus, endogenous H2S in the RVLM seems to play no role in the maintenance of basal Tb, whereas during hypoxia this gas plays a cryogenic role. Moreover, RVLM homogenates of rats exposed to hypoxia exhibited a decreased rate of H2S production. Our data are consistent with the notion that during hypoxia H2S synthesis is diminished in the RVLM facilitating hypothermia.

Endogenous hydrogen sulfide in the rostral ventrolateral medulla/Bötzinger complex downregulates ventilatory responses to hypoxia.

Hydrogen sulfide (H2S) is now recognized as a new gaseous transmitter involved in several brain-mediated responses. The rostral ventrolateral medulla (RVLM)/Bötzinger complex is a region in the brainstem that is involved in cardiovascular and respiratory functions. Recently, it has been shown that exogenous H2S in the RVLM modulates autonomic function and thus blood pressure. In the present study, we investigated whether H2S, endogenously produced in the RVLM/Bötzinger complex, plays a role in the control of hypoxia-induced hyperventilation. Ventilation (VE) was measured before and after bilateral microinjection of Na2S (H2S donor, 0.04, 1 and 2 pmol/100 nl) or aminooxyacetate (AOA, 0.2, 1 and 2 pmol/100 nl, a cystathionine ß-synthase, CBS, inhibitor) into the RVLM/Bötzinger complex followed by a 60-min period of hypoxia (7% inspired O2) or normoxia exposure. Control rats received microinjection of vehicle. Microinjection of vehicle, AOA or Na2S did not change VE in normoxic conditions. Exposure to hypoxia evoked a typical increase in VE. Microinjection of Na2S (2 pmol) followed by hypoxia exposure attenuated the hyperventilation. Conversely, microinjection of AOA (2 pmol) into the RVLM/Bötzinger complex caused an increase in the hypoxia-induced hyperventilation. Thus, endogenous H2S in the RVLM/Bötzinger complex seems to play no role in the maintenance of basal pulmonary ventilation during normoxia whereas during hypoxia H2S has a downmodulatory function. Homogenates of RVLM/Bötzinger complex of animals previously exposed to hypoxia for 60 min exhibited a decreased rate of H2S production. Our data are consistent with the notion that the gaseous messenger H2S synthesis is downregulated in the RVLM/Bötzinger complex during hypoxia favoring hyperventilation.