Vascular Biology of Hydrogen Sulfide

Indiana University, Bloomington IN

Investigators

Abstract

Long known as a toxic gas, hydrogen sulfide (H2S) has recently been shown in mammals to serve as a neurotransmitter and local signaling molecule. Recent work in this laboratory (NSF IBN-0235223) suggested that H2S impacts cardiovascular function in all vertebrates and it also led to the novel hypothesis that H2S is the heretofore elusive oxygen "sensor" producing hypoxic relaxation in systemic vessels and hypoxic constriction in pulmonary vessels. This project will examine how H2S mediates hypoxic responses in blood vessels and how this signal is transduced into contraction or relaxation. It will also determine the role of H2S in general cardiovascular function in primitive vertebrates. Electrophysiological studies on single smooth muscle cells, biochemical and biophysical studies of isolated blood vessels, and complete cardiovascular measurements on unanesthetized animals will be performed on a variety of vertebrates, from primitive hagfish to mammals. These studies will provide the first comprehensive investigation of the novel hypothesis that H2S is the key component in oxygen "sensing" in blood vessels and they will identify the phylogenetic origin and impact of H2S in the vertebrate cardiovascular system. The results will have broad implications for all of vertebrate physiology by resolving the long-standing conundrum of vascular oxygen sensing and they will provide an evolutionary window into the integrative role of H2S in the vertebrate cardiovascular system. This work is also relevant to environmental biology because H2S is often a byproduct of industrial and agricultural activity and it is potentially debilitating to aquatic vertebrates. In addition, this project will support the education of the next generation of "broad spectrum" comparative physiologists as it will provide an integrative training program from molecular biology to whole-animal physiology.