Role of Hydrogen Sulphide (H2S) on the ventilatory responses to hypercapnia

Abstract

Hydrogen sulfide (H2S), recently described as the third member of the group of gaseous transmitters, is produced endogenously by metabolic pathways with predominant participation of two enzymes: cystathionine beta-synthase (CBS ) and cystathionine gamma-lyase (CSE ). The presence and participation of CBS and CSE for generating H2S in response to hypoxia have been reported in the carotid body. However, the presence and distribution of these enzymes have not been described in specific regions of the brainstem, in particular of medullary raphe nuclei, which play an important role in ventilatory responses to hypercapnia. Since it is not known the role of endogenous H2S in the bulbar raphe on the ventilatory responses to hypercapnia, adding to the therapeutic potential for the use of this gas in clinical practice, it is extremely important to study the central mechanisms by which H2S participates in the control respiratory, in particular the aspects relating to the central chemoreception CO2/pH. Thus, this proposal aims to assess the role of H2S in the bulbar raphe on the ventilatory responses to hypercapnia. This will have three specific objectives: 1) to study the effect of microinjection in the bulbar raphe inhibitor CBS enzyme and H2S donor in ventilatory responses to hypercapnia (ventilation, O2 consumption and body temperature), 2 ) by means of immunohistochemistry, to analyze the presence and distribution of CBS enzyme in the region of bulbar raphe, as well as its co- location with serotonergic neurons in this region, which is important in central chemoreception and 3) to analyze the effect of exposure to hypercapnia on the endogenous production of H2S in the bulbar raphe. (AU)