title: The effect of sildenafil on the elasticity of erythrocytes in homozygous sickle cell disease.
abstract: OBJECTIVE
  One of the features of homozygous sickle cell disease (HbSS) is the impaired elasticity of the erythrocyte membrane that could impede microcirculatory blood flow and cause hypoxia and tissue damage. We investigated the effect of sildenafil, a phosphodiesterase 5 (PDE5) inhibitor that inhibits the breakdown of cyclic guanosine monophosphate (cGMP) resulting in vasodilatation, on the elasticity of HbSS erythrocyte.
  
  
  METHODS
  Blood samples from ten HbSS patients in steady state was exposed to different doses (5, 10, 20, and 40 μg/mL) of sildenafil and the elasticity of the erythrocytes measured at native hematocrit with the BioProfiler. An equal number of subjects with normal hemoglobin (HbAA) served as the control group.
  
  
  RESULTS
  There was a marginal increase in elasticity with 5 μg/mL of the drug and this became significant (P<0.05) with the 10 μg/mL dose. Thereafter, gradual nonsignificant decreases were observed with the 20 and 40 μg/mL doses. A similar trend was observed for the control group. The elasticity values for the HbSS subjects at native hematocrit were significantly (P<0.05) less when compared with the corresponding concentrations for the HbAA controls. This was reversed at a corrected hematocrit of 45%.
  
  
  CONCLUSIONS
  The result of this study shows that sildenafil caused an initial increase in erythrocyte membrane elasticity in both HbSS and HbAA subjects, and this later decreased with increasing concentration of the drug possibly due to the dual effect of cyclic adenosine monophosphate (cAMP).
authors: Department of Basic Medical Sciences, The University of the West Indies, Mona Campus, Kingston 7, Jamaica, West Indies.
authors: Abigail C
authors: AC
authors: Hagley
authors: Novie O
authors: NO
authors: Younger-Coleman
authors: Andrea A
authors: AA
authors: Richards
authors: Chukwuemeka R
authors: CR
authors: Nwokocha
authors: Dagogo J
authors: DJ
authors: Pepple
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000235:genetics; D004548:Elasticity; D004912:Erythrocytes / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use; D010879:Piperazines / Q000627:therapeutic use*; D011687:Purines / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate