Effect of beta-adrenergic blockers on the sickling phenomenon

Dichloroisoproterenol (DCI) and propranolol were found to inhibit sickling in vivo when they were added to red-cell suspensions prior to deoxygenation. The effectiveness was maximal between PO2's of 30 and 40 mmHg (1 mmHg = 133.322 Pa). When cells were sickled at a low oxygen tension (PO2 = 32 mmHg), and then DCI was added later, the drug decreased the degree of sickling while the suspension was maintained at the same oxygen tension. The antisickling effect of these drugs was not antagonized by isoproterenol, a beta-adrenergic stimulator, by the addition of cAMP or increase of the intracellular calcium concentration. Other beta-blockers, such as MJ1999 (sotalol) and timolol, did not show antisickling activity. It was also found that DCI, propranolol, and timolol had some effect on the delay time of gelation of sickle-cell hemoglobin (Hb S), as well as on the oxygen affinity of sickle cells.