The role of nitric oxide in regulation of deformability of red blood cells in acute phase of endotoxaemia in rats.
Using the shear stress laser diffractometer (Rheodyn) we have studied the role of nitric oxide on erythrocyte deformability during the initial 10 min after the i.v. administration of LPS at a dose of 5 mg/kg. At the stress shear force of 30 Pa the control erythrocytes elongation index (Ei) of untreated animals was 38% +/- 1.5 (mean +/- SD, n = 6) while in LPS treated animals it was decreased to 33% +/- 1.8 (n = 6) indicating significant (p < 0.01) loos of red blood cell deformability. The loss of deformability was accompanied by increased fragility of erythrocyte membranes as measured by enhanced release of free hemoglobin (E lambda 420 = 0.43 +/- 0.05 in control vs. E lambda 420 = 0.65 +/- 0.07 in LPS group) from isolated erythrocytes exposed to centrifuging at a speed of 3000 rpm for 10 min. Inhibitor of NO-synthase, NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg i.v.), significantly decreased deformability (Ei = 33.5- +/- 4.6, n = 6, p < 0.01) but did not influence fragility (E lambda 420 = 0.36 +/- 0.14, n = 6) of erythrocytes. However, when L-NAME was administered 10 min. prior to LPS it significantly improved the LPS-impaired fragility (E lambda 420 = 0.38 +/- 0.1, n = 6, p < 0.01) as compared to rats treated with LPS-alone (E lambda 420 = 0.65 +/- 0.07, n = 6). A similar protective effect of L-NAME was observed for LPS-induced impairment of erythrocyte deformability. It is concluded that NO seems to influence deformability and fragility of erythrocytes at the first stage of sepsis. During an acute phase of LPS action, possibly reflected by stimulation of endothelial constitutive (ecNOS) but not inducible NO-synthase (iNOS), the excessive amount of NO leads to a damage of erythrocyte plasticity and then the pretreatment with L-NAME exerts a protective action of LPS-impaired deformability and fragility of erythrocytes. On the other hand, basal release of NO maintains erythrocyte deformability at the physiological range and lowering of the basal level of NO by NOS-inhibitors leads to impairment or erythrocyte deformability.
Starzyk
D
D
Chair of Pharmacology, Medical College of Jagiellonian University, Cracow, Poland.
Korbut
R
R
Gryglewski
R J
RJ
D000818:Animals; D019446:Endotoxemia / Q000097:blood* / Q000139:chemically induced; D004907:Erythrocyte Deformability / Q000187:drug effects*; D004912:Erythrocytes / Q000187:drug effects* / Q000502:physiology*; D004926:Escherichia coli; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D008070:Lipopolysaccharides; D009569:Nitric Oxide