Physiologic and rheologic effects of the antisickling agent ethacrynic acid and its N-butylated derivative on normal and sickle erythrocytes.
Ethacrynic acid, a loop diuretic, has been shown to inhibit hemoglobin S polymerization. Until now, however, most studies were performed using purified solutions of hemoglobin S. The experiments reported here were designed to examine the effects of ethacrynic acid and its n-butryic acid derivative on the rheological and physiological properties of intact red blood cells. Using net and unidirectional flux measurements, both agents were shown to cause ion and water loss from normal and sickle erythrocytes. Since cell shrinkage adversely influences red cell rheology, it is unlikely that this class of compounds, despite its ability to inhibit hemoglobin S polymerization, will prove useful in the treatment of sickle cell disease.
Orringer
E P
EP
Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill 27599-7600.
Blythe
D S
DS
Whitney
J A
JA
Brockenbrough
S
S
Abraham
D J
DJ
D000755:Anemia, Sickle Cell / Q000097:blood*; D000986:Antisickling Agents / Q000009:adverse effects / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000648:ultrastructure; D004912:Erythrocytes / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D004913:Erythrocytes, Abnormal / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D004976:Ethacrynic Acid / Q000009:adverse effects / Q000494:pharmacology*; D006451:Hemoglobin, Sickle / Q000378:metabolism; D006801:Humans; D011108:Polymers; D012212:Rheology; D014882:Water-Electrolyte Balance / Q000187:drug effects
D000986:Antisickling Agents; D006451:Hemoglobin, Sickle; D011108:Polymers; D004976:Ethacrynic Acid