Effects of Neuroactive Amino Acids Derivatives on Cardiac and Cerebral Mitochondria and Endothelial functions in Animals Exposed to Stress

2017 ◽  
Vol 2 (2) ◽  
pp. 34
Author(s):  
TA Popova ◽  
II Prokofiev ◽  
IS Mokrousov ◽  
Valentina Perfilova ◽  
AV Borisov ◽  
...  

Introduction: 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.

1996 ◽  
Vol 30 (3) ◽  
pp. 118-124
Author(s):  
I. V. Volkova ◽  
I. R. Losev ◽  
V. A. Lemenkov ◽  
A. G. Mushegov ◽  
S. V. Mogil'nikov

1994 ◽  
Vol 87 (3) ◽  
pp. 303-310 ◽  
Author(s):  
S. M. Bode-Böger ◽  
R. H. Böger ◽  
A. Creutzig ◽  
D. Tsikas ◽  
F.-M. Gutzki ◽  
...  

1. L-Arginine is the physiological precursor of nitric oxide which induces vasodilatation and inhibits platelet aggregation by the formation of cyclic GMP. 2. In the present study we investigated the effects of an intravenous infusion of L-arginine (30 g, 30 min) compared with placebo on blood pressure, heart rate and peripheral haemodynamics in ten healthy male subjects. Cyclic GMP, NO−2 and NO−3 were determined in plasma and urine to assess NO production in vivo by a new, highly specific and sensitive gas chromatography-mass spectrometry method. 3. L-Arginine significantly decreased mean arterial blood pressure and increased heart rate. The effect was more pronounced on diastolic than on systolic blood pressure. This was due to a decreased peripheral arteriolar resistance, as in femoral artery Doppler sonography the arterial diameter was unchanged but blood flow was increased. These haemodynamic effects were not observed after placebo administration. 4. Urinary excretion of cyclic GMP increased by 65.4% after L-arginine and by 25.1% after placebo. Urinary NO−2 excretion was near the threshold of detection. Urinary NO−3 excretion increased by 79.7% after L-arginine. Plasma arginine levels increased nearly ten-fold after the L-arginine infusion, and plasma cyclic GMP increased by a similar rate as in urine. However, plasma NO−2 and NO−3 remained unchanged after both treatments, as did plasma α-atrial natriuretic peptide levels. 5. Platelet aggregation was inhibited by 32.7% after L-arginine (P < 0.05), but was unchanged after placebo. Platelet intracellular cyclic GMP was increased by 43.0% after L-arginine, but not after placebo (P < 0.05). 6. We conclude that intravenous L-arginine decreases peripheral arteriolar tone and inhibits platelet aggregation in healthy human subjects by enhancing nitric oxide formation and, concomitantly, cyclic GMP formation.


1989 ◽  
Vol 17 (4) ◽  
pp. 470-475 ◽  
Author(s):  
J. L. Kermode ◽  
N. J. Davis ◽  
W. R. Thompson

The Finapres (Ohmeda, Madison, U.S.A.) is a non-invasive device which continuously measures the arterial blood pressure in a finger and produces a real-time display of the arterial pressure wave. It consists of a finger cuff with an infra-red transmission plethysmograph, a servo control box and a monitor unit. The device was compared with intra-arterial pressure monitoring in twenty patients during induction of anaesthesia for elective neurosurgical procedures. The differences between the two methods were considerable, ranging from −40 mmHg to +26 mmHg for mean pressure. While the Finapres has potential as a non-invasive continuous blood pressure monitor, the current model Finapres, as supplied, displays too great a variability for it to be used as an alternative to intra-arterial pressure monitoring.


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