On the cellular mechanism for the effect of acidosis on vascular tone

The role of smooth muscle [Ca2+](i) and membrane potential for the relaxati on to hypercapnic (increased CO2) and normocapnic (unchanged CO2) acidosis is not complete understood. It is often stated that membrane hyperpolarizat ion plays an important role but this has not been vigorously tested. In thi s study we investigated isolated rat cerebral small arteries under isobaric conditions. Lumen diameter:was measured simultaneously with either [Ca2+]( i) or membrane potential, and acidosis was induced by increasing PCO2 or re ducing HCO3- of the bathing solution or by adding HCl to a nominally bicarb onate-free solution. Confocal microscopy verified loading of smooth muscle cells with fluorescent dyes. Acidosis always reduced myogenic tone at trans mural pressures between 20 and 120 mmHg. Acidification at a transmural pres sure of 40 mmHg caused an increase in diameter and a decrease in [Ca2+](i). This was also seen in the presence of L-NNA and after depolarization with 50 mM K+. The response to hypercapnic and normocapnic acidosis was similar. However, while hypercapnic acidosis caused hyperpolarization, normocapnic acidosis caused depolarization. Dilatation, decrease of [Ca2+](i) and depol arization, was also seen with reduction of pH in bicarbonate free solution. We conclude that the isobaric relaxation to both hypercapnic and normocapn ic acidosis is most likely mediated by a reduction of [Ca2+](i). Membrane p otential may on the other hand not play a major role for this reduction of [Ca2+](i) and it is possible that molecular CO2 has an effect on the membra ne potential.