To study the effects of glufimet, a new derivative of glutamic acid, and
phenibut, a derivative of γ-aminobutyric acid (GABA), on cardiac and cerebral mitochondria
and endothelial functions in animals following exposure to stress and inducible nitric oxide
synthase (iNOS) inhibition. Methods: Rats suspended by their dorsal cervical skin fold for 24
hours served as the immobilization and pain stress model. Arterial blood pressure was
determined using a non-invasive blood pressure monitor. Mitochondrial fraction of heart and
brain homogenates were isolated by differential centrifugation and analysed for mitochondrial
respiration intensity, lipid peroxidation (LPO) and antioxidant enzyme activity using
polarographic method. The concentrations of nitric oxide (NO) terminal metabolites were
measured using Griess reagent. Hemostasis indices were evaluated. Platelet aggregation
was estimated using modified version of the Born method described by Gabbasov et al.,
1989. Results: The present study demonstrated that stress leads to an elevated
concentration of NO terminal metabolites and LPO products, decreased activity of antioxidant
enzymes, reduced mitochondrial respiratory function, and endothelial dysfunction. Inhibition of
iNOS by aminoguanidine had a protective effect. Phenibut and glufimet inhibited a rise in
stress-induced nitric oxide production. This resulted in enhanced coupling of substrate
peroxidation and ATP synthesis. The reduced LPO processes caused by glufimet and
phenibut normalized the endothelial function which was proved by the absence of average
daily blood pressure (BP) elevation episodes and a significant increase in platelet aggregation
level. Conclusion: Glufimet and phenibut restrict the harmful effects of stress on the heart
and brain possibly by modulating iNOS activity