Oxygen tension regulates H2S and NO bioavailability in reciprocal manner (885.3)

Abstract

Nitric oxide and hydrogen sulfide modulate several physiological and cellular functions including vasodilation, cell proliferation and redox cell signaling. Production and bioavailability of either molecule may be influenced by oxygen tension; however, the relationship between H2S and NO bioavailability during hypoxia remains poorly understood. In this study, we examined plasma free H2S and nitrite levels in healthy volunteers exposed to high altitude. Plasma free H2S levels were significantly greater at sea level compared to high altitude (5260 meters) at 1 or 16 days; whereas, plasma nitrite levels were significantly higher at high altitude compared to sea level. After spending 7 or 21 days at low altitude, volunteers were tested again at 5260 m. On reascent, plasma free H2S levels were increased compared to initial high altitude exposure. Conversely, plasma nitrite levels were lower than high altitude exposure on reascent indicating reciprocal regulation between the gasotransmitters. Calculation of plasma free H2S to nitrite ratios revealed that high altitude acclimatization decreases the ratio of plasma free H2S to nitrite, and that on reascent H2S to nitrite ratios return to low altitude levels. In vitro cellular hypoxia studies using HUVEC revealed significant decreases in acid labile sulfide while increasing protein bound biochemical forms of sulfide. Interestingly, in vitro hypoxic challenge similarly decreased free H2S to nitrite ratios in HUVEC similar to high altitude exposure. These data demonstrate a unique reciprocal relationship between H2S and NO bioavailability during hypoxia.