ROLE OF NITRIC OXIDE METABOLITES WITHIN THE IMPACT OF THE SUB-TOXIC SUCCINAMIDES DOSES ON STATE OF HEMOSTASIS
I.А. Palagina, M.Y. Kudria, О.S. Lаlymеnkо
V.Y. Danilevsky Institute of Endocrine Pathology Problems,
AMS of Ukraine, Kharkiv
We investigated the role of changes in the endogenous
nitric oxide (NO) metabolism during the influence of
succinic acid amides as biotransformation products of an
anti-diabetic drug on the state of hemostasis. In experiment
with rats, synthetic succinamides were applied in quantities
equimolar to the sub-toxic dose of the pharmaceutical
substance. We investigated the indicators characterizing the
state of platelet and coagulation hemostasis in the blood
plasma, the content of the stable NO metabolites and the
activity of nitrogen oxide synthase (NOS) in the liver homogenate,
blood plasma and urine of rats. We found that
sub-chronic succinamides introduction reduced the nitrite
and nitrate anions concentration in the blood plasma (by
30-50 and 20-35% resp.), liver (by 16-19 and 14-18%) and
urine (by 50-70 and 38-55%). These changes were essentially
dependent on the reduction in the NOS activity (by
33%). The studied compounds showed a 1.5 fold increase
in the coagulation potential of the blood plasma and cause
a 20% boost in the aggregation of thrombocytes. Analysis
of the pair correlation coefficients showed positive association
of the changes in indicators of the NO metabolism and
hemostasis. The obtained results suggest that the registered
manifestation of the pro-coagulation and thrombogenic action
of succinamides applied in the sub-toxic doses is partially
determined by a drop of the vasoactive NO pool that in turn,
occurs due to a decline of the NOS activity.
nitric oxide; hemostasis; amides of succinic acid.
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