Interaction among Hydrogen Sulfide and Other Gasotransmitters in Mammalian Physiology and Pathophysiology

Hydrogen sulfide (H₂S), nitric oxide (NO), carbon monoxide (CO), and sulfur dioxide (SO₂) were previously considered as toxic gases, but now they are found to be members of mammalian gasotransmitters family. Both H₂S and SO₂ are endogenously produced in sulfur-containing amino acid metabolic pathway in vivo. The enzymes catalyzing the formation of H₂S are mainly CBS, CSE, and 3-MST, and the key enzymes for SO₂ production are AAT1 and AAT2. Endogenous NO is produced from L-arginine under catalysis of three isoforms of NOS (eNOS, iNOS, and nNOS). HO-mediated heme catabolism is the main source of endogenous CO. These four gasotransmitters play important physiological and pathophysiological roles in mammalian cardiovascular, nervous, gastrointestinal, respiratory, and immune systems. The similarity among these four gasotransmitters can be seen from the same and/or shared signals. With many studies on the biological effects of gasotransmitters on multiple systems, the interaction among H₂S and other gasotransmitters has been gradually explored. H₂S not only interacts with NO to form nitroxyl (HNO), but also regulates the HO/CO and AAT/SO₂ pathways. Here, we review the biosynthesis and metabolism of the gasotransmitters in mammals, as well as the known complicated interactions among H₂S and other gasotransmitters (NO, CO, and SO₂) and their effects on various aspects of cardiovascular physiology and pathophysiology, such as vascular tension, angiogenesis, heart contractility, and cardiac protection.