Effect of sodium para-aminosalicylate on oxygen affinity in normal, sickle and fetal human blood

Sodium para-aminosalicylate (sodium salt of 2-hydroxy-4-aminobenzoic acid, Na-PAS) lowers the oxygen affinity of normal adult human placental, heterozygous and homozygous sickle cell anemic whole blood at 37 degrees C. The reduction of oxygen affinity is related to the type of hemoglobin in the blood. The mean P50 +/- S.E. at pH 7.40 for normal, placental, heterozygoud and homozygous sickle cell anemic blood in 26.2 +/- 0.1, 20.8 +/- 0.3, 26.8 +/- 0.3 and 31.0 +/- 0.5 mm Hg; in the presence of 5.7 mmol of Na-PAS per liter of blood the P50 values are increased to 28.0 +/- 0.3, 22.9 +/- 0.8, 30.5 +/- 0.6 and 33.9 +/- 0.3 mm Hg, respectively. The Bohr effect in normal and placental blood at this Na-PAS concentration is essentially unchanged: in heterozygous and homozygous sickle cell anemic blood, the Bohr factor (deta log P50/deta pH) is reduced from -0.48 +/- 0.02 to -0.41 +/- 0.01 and from -0.53 +/- 0.03 to -0.48 +/- 0.01. The Hill constants (n) of normal and placental blood are not affected by Na-PAS. In homozygous and heterozygous sickle blood, high concentrations of Na-PAS (22.9 mmol/l) decrease the Hill constant from 2.55 to 2.35 and from 2.56 to 2.28, respectively. Na-PAS is more firmly bound to red blood cells than to plasma. The binding of Na-PAS is probably primarily ionic in nature since the drug can be almost completely removed from blood components by dialysis. The changes in oxygen affinity caused by Na-PAS are consistent with conformational changes (R leads to T) which enhance the presence of deoxyhemoglobin.