The effect of prostacyclin and nitric oxide on deformability of red blood cells in septic shock in rats.

Six hours after administration of E. Coli endotoxin (LPS) into rats (10 mg kg-1, i.p.) a significant (P < 0.001) decline in the red blood cell deformability index (RBC Dj) was observed. The control Di value of untreated animals it was 300 +/- 39 RBC x 10(6)/min (means +/- S.D.; n = 12) while in LPS treated animals was 140 +/- 50 RBC x 10(6)/min; n = 12. Pretreatment of the animals with the stable analogue of prostacyclin, iloprost (30 micrograms/kg, i.p.) or with the inhibitor of thromboxane A2-synthase, camonagrel (10 mg/kg, i.p.), but not with nitric oxide donor, such as GEA 5285 (10 mg/kg, i.p.), significantly increased deformability of red blood cells in the group of non-septicaemic animals, and antagonized the LPS-induced decline in red blood cell deformability of septicaemic rats. Administration of NG-nitro-L-arginine (L-NNA, 30 mg/kg, i.p.), as that of aspirin (50 mg/kg, i.p.), did not affect red blood cell deformability in non-septicaemic rats, however, in contrast with aspirin, it significantly improved deformability of red blood cells in LPS-treated animals. It is concluded that prostacyclin, camonagrel and L-NNA can act as protective agents against LPS-induced loss of red blood cell deformability. The mechanisms of this protection are complex and, possibly, related to the specific effects of these agents on biochemical function of leukocytes present in RBC suspension. While the effect of exogenous prostacyclin (iloprost) may be explained on the basis of its direct cytoprotective potency on leukocytes, the effect of camonagrel is indirect and can be attributed both to the release of endogenous prostacyclin and to the inhibition of thromboxane A2-synthase. The protection induced by NO-synthase inhibitor seems to depend upon inhibition of an increase of the generation of nitric oxide which follows administration of LPS.