[Role of restricted nitric oxide overproduction in the cardioprotective effect of adaptation to intermittent hypoxia].

Adaptation to intermittent normobaric hypoxia is cardioprotective and can stimulate nitric oxide (NO) synthesis. However the role of nitric oxide (NO) in prevention of ischemia-reperfusion (IR) injury of myocardium is controversial. This study was focused on evaluating the effect of adaptation to hypoxia and IR on NO production and development of nitrative stress in the myocardium. Adaptation to hypoxia tended to increase NO production, which was determined by the total level of plasma nitrite and nitrate, and prevented IR-induced NO overproduction. The IR-induced NO overproduction was associated with significant 3-nitrotyrosine (3-NT) accumulation in the left ventricle but not in septum or aorta. In hypoxia-adapted rats, 3-NT after IR was similar to that of control rats without IR. IHC induced marked accumulation of HIF-1alpha in the left ventricle. We suggest that HIF-1alpha contributes to NO-synthase expression during adaptation to hypoxia and thereby facilitates the increase in NO production. NO, in turn, may subsequently prevent NO overproduction during IR by a negative feedback mechanism.

[Prevention of the brain neurodegeneration in rats with experimental Alzheimer's disease by adaptation to hypoxia].

The study focused on a possibility of preventing brain neurodegeneration by adaptation to intermittent hypoxia (AH) in rats with experimental Alzheimer's disease (AD) modeled by injection of a neurotoxic bert-amyloid peptide fragment (Ab) into n. basalis magnocellularis. AH was produ- ced in an altitude chamber (4.000 m; 4 hours daily; 14 days). The following results were obtained after fifteen days of the Ab injection: (1) AH substantially prevented the memory impairment induced by Ab, which was determined using the conditioned avoidance reflex test; (2) the AH significantly restricted the enhanced oxidative stress, which was determined spectrophotometrically by thiobarbituric acid-reactive substance level in the hippocampus; (3) the AH completely prevented Ab-induced nitric oxide (NO) overproduction in brain, which was measured by tissue level of nitrite and nitrate; (4) pathologically changed and dead neurons (Niessle staining) were absent in the brain cortex of rats exposed to AH before the Ab injection. Therefore AH seems to effectively prevent oxidative and nitrosative stress thereby providing protection of brain against neurodegeneration and preservation of cognitive function in experimental AD.

[Correction of NO-dependent cardiovascular disorders by adaptation to hypoxia]. / Korrektsiia NO-zavisimykh serdechno-sosudistykh narushenii s pomoshch'iu adaptatsii k gipoksii.

Spontaneously hypertensive rats (SHR-SP) were adapted to intermittent hypobaric hypoxia in an altitude chamber for 40 days. The adaptation to hypoxia prevented an excessive endothelium-dependent relaxation and hypotension characteristic of myocardial infarction. The adaptation also attenuated the increase in blood pressure and prevented impairment of the endothelium-dependent relaxation in SHR-SP. The universal nature of the adaptation allows to use it for correcting many cardiovascular disorders related to diverse alterations of NO metabolism.

[The role of preventing nitric oxide deficiency in the antihypertensive effect of adaptation to hypoxia]. / Rol' preduprezhdeniia defitsita oksida azota v antigipertenzivnom éffekte adaptatsii k gipoksii.

Shortage of endothelial nitric oxide (NO) manifested as decreased daily urinary excretion of nitrate and nitrite as well as attenuated endothelium-dependent relaxation of conduit and resistance vessels progresses with age-related increase of blood pressure (BP) in stroke-prone spontaneously hypertensive rats (SHRSP). Simultaneous NO-dependent suppression of vascular contractions is, apparently, due to the inducible NO synthase activity in vascular smooth muscle specific for spontaneously hypertensive rat. Adaptation of rats to hypobaric hypoxia initiated at early hypertensive stage (at the age of 5-6 weeks) decelerates hypertension progress. The antihypertensive effect of the adaptation was accompanied by stimulation of endothelial NO synthesis and prevention of impaired NO-dependent response in isolated blood vessels. Nitric oxide stores were formed in the vascular wall of SHRSP and WKY rats at the same time. The obtained data indicate a significant role of correction of endothelial NO deficiency in the antihypertensive effect of adaptation to hypoxia.

[The production and deposition of nitric oxide during adaptation to hypoxia]. / Produktsiia i deponirovanie oksida azota pri adaptatsii k gipoksii.

It is common knowledge that adaptation to hypobaric hypoxia provides for a number of protective NO-dependent effects in the organism. However, many aspects of its influence on NO metabolism remain unclear. In this work we studied the relationship between NO production and deposition in the course of adaptation to hypoxia. No production was assayed by the total concentration of nitrates and nitrites in rat serum, while the volume of NO depot was determined from the level of isolated aorta relaxation in response to diethyldithiocarbamate in vitro. In the course of adaptation to hypoxia, nitrate and nitrite concentration increases as well as NO deposition in the vascular wall. The volume of NO depot correlated reliably with the serum concentration of nitrates and nitrites. Hence, adaptation to hypoxia increases NO production and deposition, which can underlie its NO-dependent protective effects.

[Prevention of nitric oxide hyperproduction by adaptation to stressor effects]. / Preduprezhdenie giperproduktsii oksida azota s pomoshch'iu adaptatsii k stressornym vozdeistviiam.

As was shown earlier, acute hypotensive shock induced by nitrogen oxide (NO) hyperproduction can be prevented by dosed adaptation to environmental factors. In this work we tested the hypothesis that the mechanism of this adaptive effect is based on limiting NO hyperproduction. It was shown that rat adaptation to stress completely prevented arterial depression and sharply increased revival rate of the animals after heat shock. Hypotension induced by heat shock was accompanied by almost 2.5-fold increase in NO production (EPR analysis) as compared to the control. At the background of preadaptation, heat shock did not increase NO production relative to the animals not subjected to heat shock. The data obtained agree with the proposal that the adaptation initiates NO-dependent mechanisms of limiting NO hyperproduction. Such limiting seems to be negatively regulated by NO.

[The effect of adaptation to a course of stress-inducing electrostimulation on the reactivity of an isolated resistive artery]. / Vliianie adaptatsii k kursu stressindutsiruiushchei élektrostimuliatsii na reaktivnost' izolirovannoi rezistivnoi arterii.

Repeated stress adaptation made with a course of electrostimulation was found to result in changes in the responsiveness of the rat isolated tail artery taken from adapted animals. These changes appeared as decreased vasoconstrictive responses to norepinephrine and significantly higher endothelium-dependent vasodilation induced by acetylcholine and the beta-agonist isoproterenol. The regulatory shift occurred towards vasodilation of the resistive artery makes the studies of the impact of stress adaptation on blood pressures in hypertension promising.

[Decrease in constrictor response and increase in dilator response of the resistant artery in experimental myocardial infarction: effect of adaptation to hypoxia on this phenomenon]. / Umen'shenie konstriktornykh i uvelichenie dilatatornykh reaktsii rezistivnoi arterii pri éksperimental'nom infarkte miokarda, vliianie adaptatsii k gipoksii na étot fenomen.

After adaptation to hypoxia experimental myocardial infarction does not result in enhanced vasodilatory responses of isolated tail artery from rat to acetylcholine and isoproterenol. At the same time the vascular reactivity to norepinephrine and phenylephrine is enhanced. These data may explain the previously described improvement in postinfarction time course of the blood pressure due to preliminary adaptation to hypoxia.

[Adaptation to periodic hypoxia decreases vasoconstrictor and increases vasodilator responses of resistant arteries]. / Adaptatsiia k periodicheskoi gipoksii snizhaet konstriktornye i povyshaet dilatatornye reaktsii rezistivnoi arterii.

Adaptation to intermittent hypoxia resulted in reduced vasoconstrictor responses of rat tail artery elicited by sympathetic nerve stimulation due to desensitization of alpha- and activation beta 2-adrenoceptors. Endothelium-dependent relaxation was enhanced under the impact of adaptation to intermittent hypoxia. These shifts may play a part in antihypertensive effect of adaptation to hypoxia which has been proved earlier.

[Effect of fish oil with a high content of polyunsaturated fatty acids (eiconole) on myogenic tone and magnitude of the constrictor and dilator responses in isolated tail artery of rats]. / Vliianie ryb'ego zhira s vysokim soderzhaniem polinenasyshchennykh zhirnykh kislot (éikonola) na miogennyi tonus i velichinu konstriktornykh i dilatatornykh reaktsii izolirovannoi khvostovoi arterii krysy.

A long-term excess of polyunsaturated fatty acids in diet resulted in more than twofold reduced myogenic tone of isolated rat tail artery. Vasoconstrictory responses to norepinephrine and phenylephrine were reduced as well. At the same time the excess of dietary polyunsaturated fatty acids resulted in enhanced vasodilatory responses to isoproterenol and acetylcholine. This complex of universally targeted shifts may play a significant part in the antihypertensive effect of excessive polyunsaturated fatty acids in diet.

[The suppression of neurogenic vascular reactions by a factor released into the blood during immobilization stress]. / Ugnetenie neirogennykh sosudistykh reaktsii faktorom, vydeliaiushchimsia v krov' pri immobilizatsionnom stresse.

In isolated segment of the rat tail artery perfused with the animal donor's blood the effect of suppression of neurogenic vascular tonus, in immobilization of the animal donor, was found in 80% of cases. In 62% of cases, the suppression occurred at the beginning of the immobilization and seemed to be due to the effect of hypothetical humoral factor on the synapse area. In 38% of cases, the suppression started within 30-40 min of the immobilization start and had a different cause. The adaptive significance of these responses is discussed.