Highlights in basic autonomic neurosciences: central adenosine A1 receptor - the key to a hypometabolic state and therapeutic hypothermia?

The positive outcome that hypothermia contributes to brain and cardiac protection following ischemia has stimulated research in the development of pharmacological approaches to induce a hypothermic/hypometabolic state. Here we review three papers to highlight the role of the adenosine 1 receptor (A1AR) as a potential mediator and physiological regulator of a hypothermic state in both hibernating and non-hibernating mammals. We would like to emphasize the importance of comparative studies between hibernating and non-hibernating species that could lead to important discoveries on the mechanisms inducing hibernation and how they might be translated to induce a clinically useful hypothermic state.

Cutaneous vasodilation elicited by disinhibition of the caudal portion of the rostral ventromedial medulla of the free-behaving rat.

Putative sympathetic premotor neurons controlling cutaneous vasomotion are contained within the rostral ventromedial medulla (RVMM) between levels corresponding, rostrally, to the rostral portion of the nucleus of the facial nerve (RVMM(fn)) and, caudally, to the rostral pole of the inferior olive (RVMM(io)). Cutaneous vasoconstrictor premotor neurons in the RVMM(fn) play a major role in mediating thermoregulatory changes in cutaneous vasomotion that regulate heat loss. To determine the role of neurons in the RVMM(io) in regulating cutaneous blood flow, we examined the changes in the tail and paw skin temperature of free-behaving rats following chemically-evoked changes in the activity of neurons in the RVMM(io). Microinjection of the GABA(A) agonist, muscimol, within either the RVMM(fn) or the RVMM(io) induced a massive peripheral vasodilation; microinjection of the GABA(A) antagonist bicuculline methiodide within the RVMM(fn) reversed the increase in cutaneous blood flow induced by warm exposure and, unexpectedly, disinhibition of RVMM(io) neurons produced a rapid cutaneous vasodilation. We conclude that the tonically-active neurons driving cutaneous vasoconstriction, likely sympathetic premotor neurons previously described in the RVMM(fn), are also located in the RVMM(io). However, in the RVMM(io), these are accompanied by a population of neurons that receives a tonically-active GABAergic inhibition in the conscious animal and that promotes a cutaneous vasodilation upon relief of this inhibition. Whether the vasodilator neurons located in the RVMM(io) play a role in thermoregulation remains to be determined.