Effect of Extracellular Acidosis on Functional Contribution of K_ATP and TASK-1 Potassium Channels to Vascular Tone Regulation in Early Postnatal Ontogenesis

Activity of many proteins and hence of the mechanisms of vasculartone regulation depend on medium acidity. A decrease of pH (in uncompensatedacidosis) typically causes vasorelaxation of blood vessels, whichis studied in sufficient detail in an adult organism. However, theeffect of acidosis on the mechanisms of vascular tone regulationin the early postnatal period remains almost completely unexplored.The aim of this work was to study the effect of extracellular metabolicacidosis on the functional contribution of K_ATP andTASK-1 potassium channels to vascular tone regulation in the early postnatalperiod. We modeled uncompensated extracellular metabolic acidosis(pH 6.8, equimolar NaHCO₃ substitution ina solution for NaCl) and studied isometric contractile responsesof the saphenous artery in adult rats aged 3–4 months and rat pupsaged 12–15 days. Arterial contraction to the α₁-adrenergicagonist methoxamine at pH 6.8 was reduced compared to normal pH7.4 in both 3–4-month- and 12–15-day-old rats. The K_ATP channelblocker glibenclamide did not alter arterial responses to methoxamineat either pH 7.4 or pH 6.8 in both age groups. The TASK-1 channelblocker AVE1231 did not alter arterial contractile responses atany pH in 3–4-month-old rats. However, in 12–15-day-old rat pups,the AVE1231-induced increase in contractile responses to methoxaminewas less at pH 6.8 than at pH 7.4. Thus, acidosis reduces arterialcontractile activity in both 3–4-month-old rats and animals in earlypostnatal ontogenesis, while in the latter, the anticontractilerole of TASK-1 channels decreases, and K_ATP channelsdo not affect vascular tone regulation at either normal or acidic pHvalues in any of the age groups.