The influence of cooling and TRPM8 ion channel activation on the level of pro-inflammatory cytokines in normotensive and hypertensive rats.

The role of thermosensitive TRP ion channels in physiological processes in the whole organism is far from being clear. In present work we tried to understand the possible participation of the cold-sensitive ion channel TRPM8 in regulation of the pro-inflammatory cytokine level in blood, and to see if hypertension (widely spread disease) changes this relationship. Experiments were carried out on normotensive Wistar rats and rats with inherited stress-induced arterial hypertension. The effects of deep rapid and slow cooling with decrease in rectal temperature by 3°C, and activation of the skin TRPM8 ion channel by its agonist menthol (application of 1% L-menthol) on the concentration of pro-inflammatory cytokines (IL-6, IL-1β and TNFα) in blood have been studied. The data have shown that the TRPM8 ion channel participates in regulation of pro-inflammatory cytokine in the whole organism, as well as exposure to cold. In normotensive animals the activation of the cold-sensitive TRPM8 ion channel in skin by its agonist menthol without any temperature shifts causes an increase (about two fold) of pro-inflammatory cytokines IL-6 and IL-1 β in blood without any changes in the level of TNFα. The effect of cooling (slow or rapid) on IL-6 and IL-1β is comparable with the effect of the TRPM8 activation. The changes in TNFα concentration were observed only at slow cooling. In hypertensive rats there were no changes in the level of pro-inflammatory cytokines under the effect of cooling or activation of the TRPM8 ion channel. This evidences for the decrease in TRPM8 activity under arterial hypertension. One of possible mechanisms of profound changes at arterial hypertension may be the alteration in activity of some ion channels, and TRPM8 is one of them.