Central hydrogen sulphide mediates ventilatory responses to hypercapnia in adult conscious rats

Aim Hydrogen sulphide (H 2 S) is endogenously produced and plays an important role as a modulator of neuronal functions; however, its modulatory role in the central CO 2 chemoreception is unknown. The aim of the present study was to assess the role of endogenously produced H 2 S in the ventilatory response to hypercapnia in adult conscious rats. Methods Cystathionine β ‐synthase ( CBS ) and cystathionine γ ‐lyase ( CSE ) inhibitors (aminooxyacetate: AOA and propargylglycine: PAG respectively) and a H 2 S donor (sodium sulphide: Na 2 S) were microinjected into the fourth ventricle (4V). Ventilation ( V ˙ E ), oxygen consumption ( V ˙ O 2 ) and body temperature were recorded before (room air) and during a 30‐min CO 2 exposure (hypercapnia, 7% CO 2 ). Endogenous H 2 S levels were measured in the nucleus tractus solitarius ( NTS ). Results Microinjection of Na 2 S (H 2 S donor), AOA ( CBS inhibitor) or PAG ( CSE inhibitor) did not affect baseline of the measured variables compared to control group (vehicle). In all experimental groups, hypercapnia elicited an increase inV ˙ E . However, AOA microinjection, but not PAG , attenuated the ventilatory response to hypercapnia ( P  < 0.05), whereas Na 2 S elicited a slight, not significant, enhancement. Moreover, endogenous H 2 S levels were found higher in the NTS after hypercapnia ( P  < 0.05) compared to room air (normoxia) condition. Conclusion There are a few reports on the role of gaseous transmitters in the control of breathing. Importantly, the present data suggest that endogenous H 2 S via the CBS –H 2 S pathway mediates the ventilatory response to hypercapnia playing an excitatory role.