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

Activity of many proteins and hence of the mechanisms of vascular tone regulation depend on medium acidity. A decrease of pH (in uncompensated acidosis) typically causes vasorelaxation of blood vessels, which is studied in sufficient detail in an adult organism. However, the effect of acidosis on the mechanisms of vascular tone regulation in the early postnatal period remains almost completely unexplored. The aim of this work was to study the effect of extracellular metabolic acidosis on the functional contribution of K-ATP and TASK-1 potassium channels to vascular tone regulation in the early postnatal period. We modeled uncompensated extracellular metabolic acidosis (pH 6.8, equimolar NaHCO3 substitution in a solution for NaCl) and studied isometric contractile responses of the saphenous artery in adult rats aged 3-4 months and rat pups aged 12-15 days. Arterial contraction to the alpha(1)-adrenergic agonist methoxamine at pH 6.8 was reduced compared to normal pH 7.4 in both 3-4-month- and 12-15-day-old rats. The K-ATP channel blocker glibenclamide did not alter arterial responses to methoxamine at either pH 7.4 or pH 6.8 in both age groups. The TASK-1 channel blocker AVE1231 did not alter arterial contractile responses at any pH in 3-4-month-old rats. However, in 12-15-day-old rat pups, the AVE1231-induced increase in contractile responses to methoxamine was less at pH 6.8 than at pH 7.4. Thus, acidosis reduces arterial contractile activity in both 3-4-month-old rats and animals in early postnatal ontogenesis, while in the latter, the anticontractile role of TASK-1 channels decreases, and K-ATP channels do not affect vascular tone regulation at either normal or acidic pH values in any of the age groups.