167.
WAYS OF MYOCARDIAL METABOLIC DISORDERS CORRECTION AT HYPOXIA BY
NEW PHARMACOLOGICAL PREPARATIONS. Gonchar Olga
1
, Klyuchko Elena
2
, Beloshitsky
Pavel
2
. Bogomoletz Institute of Physiology, NAS Ukraine
1
, Medical and Biological Station, NAS
Ukraine
2
.
It is known that development of hypoxic state is followed by the strengthening of free-radical
processes, disorders in prooxidant- antioxidant balance, metabolic changes in tissues and the
search of new medicines for hypoxic states correction (our aim) is an actual task for today. We
studied the influence of yackton (succinic acid derivative) and splenoside (nonprotein factor from
the spleen with nucleoside complex as active base) on enzymatic and non- enzymatic antioxidant
system activities in myocardium at the level of lipid peroxidation (LPO) in experiments on rats
exposed to hypoxic gas conditions (7% O2). Preliminary administration of the tested drugs
prevented the heart hypoxic damage. Were found that all agents reduce LPO, increase activities
of superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase as well as
increase of reduced glutathione content in comparison with hypoxia state. NAD/NADH rate
increased and decreased lactate/ pyruvate rate and lactate dehydrogenase activation. After the
splenoside injection in hypoxia conditions we registered significant activation of glucoso-6-
phosphatedehydrogenase (the first and the rate-limiting enzyme of the pentose phosphate
pathway). After the yackton treatment we registered significant increase of succinate
dehydrogenase activity in mitochondria. Were shown possible ways of metabolic change
corrections in myocardium in conditions of non-sufficient tissue oxygen supply using
pharmaceutical preparations through the electron transport intensification and recovery of energy
functions in mitochondria, as well as maintaining of glutathione recycling activity through the
stimulation of the pentose phosphate pathway, enhance of intracellular NADPH stores.
168.
GENOMICS OF HIGH-ALTITUDE ADAPTATION AND MALADAPTATION. M A Qadar
Pasha
1
. Institute of Genomics & Integrative Biology, Delhi, India
1
.
Maladaptation to the hypoxic environment at high-altitude (HA), while render the
performance of sojourners difficult, hardly affects the routine physical activities of the natives
because of adaptation to the environment. Acquisition of HA phenotype over the generations by
natural selection is a possible explanation. Selection of the genes of Renin-Angiotensin-
Aldosterone System (RAAS) and Kallikrein-Kinin System (KKS) is the manifestation of their
importance in blood pressure homeostasis, which is of utmost importance at HA. The repertoire
of our research included the possibility of association of all the potential polymorphisms reported
in the genes of these systems and the hunt for novel variations. The polymorphisms included in
the study were I/D in Angiotensin-converting enzyme (ACE), M235T, T174M, GT-repeat in
Angiotensinogen (AGT), A1166C in Angiotensin II receptor1, Intron-2 conversion, Arg173Lys, -
344T/C in Aldosterone synthase (CYP11B2) in RAAS and CA-repeat, G894T, 4B/4A, -922A/G,
-786T/C in endothelial nitric oxide synthase (eNOS), CA- and AAT-repeats in neuronal NOS
(nNOS) in KKS. Our results revealed a significant association of alleles such as I of ACE, T174
of AGT, shorter CA-repeats (14-25), G894, 4B, -922A, -786T of eNOS with adaptation that may
facilitate routine physical activities at HA. On the other hand, alleles like D of ACE, M174 of
AGT, Intron-2 conversion of CYP11B2, longer CA-repeats (34-45), T894, 4A of eNOS
associated with high altitude pulmonary edema and hypertension. ACE activity, aldosterone and
NO levels showed correlation with respective alleles. Novel variations, 5'UTR 1598C/T, Exon 1
1773C/T and Intron 1 GT- and CA-repeats and Intron 3 GT-repeat in inducible NOS have also
been scored. The inference drawn is that several markers in few of these genes are in the process
of natural selection for HA environment, while few associate with HA disorders. The outcome
may find application in predisposition to HA disorders.
169.
PROBLEM OF COMPLEX INFLUENCES OF HYPOXYBARIA AND OTHER FACTORS ON
ORGANISM. Beloshitsky Pavel
1
. Medical and Biological Station, NAS Ukraine
1
.
