Induction of a Torpor-Like State by 5’-AMP Does Not Depend on H(2)S Production

BACKGROUND: Therapeutic hypothermia is used to reduce ischemia/reperfusion injury (IRI) during organ transplantation and major surgery, but does not fully prevent organ injury. Interestingly, hibernating animals undergo repetitive periods of low body temperature called ‘torpor’ without signs of organ injury. Recently, we identified an essential role of hydrogen sulfide (H(2)S) in entrance into torpor and preservation of kidney integrity during hibernation. A torpor-like state can be induced pharmacologically by injecting 5’-Adenosine monophosphate (5’-AMP). The mechanism by which 5’-AMP leads to the induction of a torpor-like state, and the role of H(2)S herein, remains to be unraveled. Therefore, we investigated whether induction of a torpor-like state by 5-AMP depends on H(2)S production. METHODS: To study the role of H(2)S on the induction of torpor, amino-oxyacetic acid (AOAA), a non-specific inhibitor of H(2)S, was administered before injection with 5'-AMP to block endogenous H(2)S production in Syrian hamster. To assess the role of H(2)S on maintenance of torpor induced by 5’-AMP, additional animals were injected with AOAA during torpor. KEY RESULTS: During the torpor-like state induced by 5’-AMP, the expression of H(2)S- synthesizing enzymes in the kidneys and plasma levels of H(2)S were increased. Blockade of these enzymes inhibited the rise in the plasma level of H(2)S, but neither precluded torpor nor induced arousal. Remarkably, blockade of endogenous H(2)S production was associated with increased renal injury. CONCLUSIONS: Induction of a torpor-like state by 5’-AMP does not depend on H(2)S, although production of H(2)S seems to attenuate renal injury. Unraveling the mechanisms by which 5’-AMP reduces the metabolism without organ injury may allow optimization of current strategies to limit (hypothermic) IRI and improve outcome following organ transplantation, major cardiac and brain surgery.