Hydrogen sulfide and oxygen sensing: implications in cardiorespiratory control

Abstract

Although all cells are variously affected by oxygen, a few have the responsibility of monitoring oxygen tensions and initiating key homeostatic responses when P(O2) falls to critical levels. These ;oxygen-sensing' cells include the chemoreceptors in the gills (neuroepithelial cells), airways (neuroepithelial bodies) and vasculature (carotid bodies) that initiate cardiorespiratory reflexes, oxygen sensitive chromaffin cells associated with systemic veins or adrenal glands that regulate the rate of catecholamine secretion, and vascular smooth muscle cells capable of increasing blood flow to systemic tissues, or decreasing it through the lungs. In spite of intense research, and enormous clinical applicability, there is little, if any, consensus regarding the mechanism of how these cells sense oxygen and transduce this into the appropriate physiological response. We have recently proposed that the metabolism of hydrogen sulfide (H2S) may serve as an 'oxygen sensor' in vertebrate vascular smooth muscle and preliminary evidence suggests it has similar activity in gill chemoreceptors. In this proposed mechanism, the cellular concentration of H2S is determined by the simple balance between constitutive H2S production in the cytoplasm and H2S oxidation in the mitochondria; when tissue oxygen levels fall the rate of H2S oxidation decreases and the concentration of biologically active H2S in the tissue increases. This commentary briefly describes the oxygen-sensitive tissues in fish and mammals, delineates the current hypotheses of oxygen sensing by these tissues, and then critically evaluates the evidence for H2S metabolism in oxygen sensing.