EFFECT OF PROPRANOLOL UPON EFFECT THE HEMOGLOBIN-OXYGEN DISSOCIATION CURVE

¹ Smith Kline and French Laboratories, Philadelphia, Pennsylvania

Propranolol (1-5 x 10^-4 M) was found to shift the hemoglobin-oxygen dissociation curve of human erythrocytes significantly to the right; the mean p50 was increased in various studies by 6 to 8 mm Hg. The dissociation curve was measured in vitro on freshly obtained, washed red blood cells previously incubated for 90 minutes in physiological buffer (pH 7.4, T = 37°C) which contained the test compound. Concomitant with shifting the curve, propranolol also altered the morphology of the red blood cells and reduced the hematocrit. d-Propranolol was more effective than the l-form in shifting the curve and INPEA, MJ 1999 and Kö 592 were ineffective at 5 x 10^-4 M, indicating the effect was not beta receptor mediated. Propranolol did not affect the dissociation curve of dialyzed hemoglobin or of erythrocytes obtained from out-dated blood. Biochemically, the drug significantly decreased the erythrocyte content of 2,3-diphosphoglyceric acid and adenosine triphosphate and inhibited glucose utilization by 60%. The onset of propranolol action on cellular morphology and the dissociation curve was essentially instantaneous and peaked within approximately 20 minutes which suggests these effects may be membrane mediated.

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