Enhanced affinity for arachidonic acid in platelet-rich plasma from rats with Adriamycin-induced nephrotic syndrome.

We have measured the response to arachidonic acid (AA) in platelet-rich plasma (PRP) of rats with Adriamycin-induced nephrotic syndrome. For this purpose we measured the kinetics of generation of malondialdehyde (MDA), a stable product of cyclooxygenase activity, in response to platelet stimulation with different concentrations of the substrate. The apparent Km of platelet cyclo-oxygenase for AA was similar in PRP from control rats and rats treated 1-5 days previously, whereas it was significantly reduced, as compared to controls, in PRP of rats treated 2-5 weeks previously. Such a difference was not observed when washed platelet suspensions were tested instead of PRP. Experiments with crossed platelet/plasma systems indicated that in rats treated from 2-5 weeks, a plasmatic abnormality was indeed responsible for the increased affinity of platelets for AA. It is conceivable that in this nephrotic syndrome model characterized by heavy proteinuria, some plasmatic component would be lost with the urine which is normally modulating the platelet response to AA. The observed increase in platelet affinity for AA could at least partially contribute to the enhanced thrombotic tendency reported in the same experimental model.