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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2019; 65(6): 12-21


AMINOGUANIDINE RESTORES ENDOGENOUS HYDROGEN SULFIDE SYNTHESIS, CONSTITUTIVE NITRIC OXIDE SYNTHESIS, ENDOTHELIUM-DEPENDENT VASODILATION AND INHIBITS MITOCHONDRIAL PERMEABILITY TRANSITION PORE OPENING IN THE HEART OF OLD RATS

N.A. Strutynska, Yu.V. Korkach, L.A. Mys, A.Yu. Luchkova, V.F. Sagach

    Bogomoletz Institute of Physiology of NAS of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz65.06.012

Abstract

It has been shown that the development of aging is accompanied by a significant decrease in the activity of constitutive Ca2+/calmodulin-dependent NO-synthase (cNOS) against the increasing of an inducible calcium-dependent synthesis of nitric oxide (iNOS) and formation of oxidative stress markers (superoxide radical, diene conjugates and malonic dialdehyde). The use of aminoguanidine as an iNOS inhibitor (20 mg/kg) significantly reduced iNOS activity, leading to the restoration of constitutive NO synthesis in the cardiovascular system of old animals. In doing so, we observed an activation of endogenous hydrogen sulphide (H2S) synthesis, which is a potent lipophilic antioxidant and a biological modulator of some enzymes. Thus, its content in the blood plasma of old rats was restored to the same values as in adult rats and amounted to 2.36±0.12 nmol/mg of protein, and the values of mitochondrial hydrogen sulfide increased 1.5 times (4.32±0.23 nmol/mg of protein) compared with adult animals (2.78 ± 0.18 nmol/mg of protein). The increase in constitutive synthesis of NO and H2S, well known modulators of nonspecific mitochondrial permeability transition pore (mPTP) opening, led to a decrease in its sensitivity to Ca2 +. This was characterized by an increase in the threshold concentration of the inducer which leads to swelling of the mitochondria of the heart in old animals. The protective effects of aminoguanidine were also manifested in a significant increase (almost threefold) in the aortic relaxation amplitude in old rats (26.4±2.8%) if compared with old animals (9.6±2.6%). This indicates the recovery of decreased endothelial function in old rats. Thus, the use of aminoguanidine in old rats led to an increase in the constitutive nitric oxide and endogenous hydrogen sulfide synthesis against the slowing oxidative processes, which contributed to the inhibition of mPTP in the heart and the restoration of endothelium-dependent relaxation of aortic vessels

Keywords: aminoguanidine; cNOS; hydrogen sulphide; mPTP; vasodilation

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