Effect of propranolol on oxygen binding to hemoglobin in vitro and in vivo.

We have shown that propranolol reduces oxygen binding by hemoglobin in intact red cells by increasing the selective permeability of the red cell membrane resulting in an exodus of potassium, chloride, and water. The latter effects result in a new distribution of hydrogen ion between cell and plasma, and thereby a reduction in red cell pH. The reduction in pH can fully explain the change in hemoglobin's affinity for oxygen based on the Bohr effect. Either Dor DL-propranolol can produce the change in red cell pH and oxygen binding by hemoglobin. The drug action on permeability is not prevented by epinephrine, although it is by chlorbutanol. Hence, the membrane action of propranolol does not appear to be related to its activity as a beta-adrenergic receptor blocking agent. Propranolol produced a marked alteration in red cell shape as well as in hydration (hypovolumic stomatocytes). The two effects were separable since dehydration of the cell by the addition of sucrose to plasma did not result in stomatocytes and chlorbutanol blocked the enhancement of permeability of the red cell membrane by propranolol without preventing the shape change (isovolumic stomatocytes). This suggests that propranolol may have two separate sites of membrane interaction. Propranolol (10 to 360 mg) administered to human subjects did not affect hemoglobin-oxygen affinity. This is explained by the fact that the concentration in blood after such doses is nearly 4,000 to 100-fold lower than that required to achieve changes in blood in vitro.