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Prenatal hypoxia during the prenatal period can interfere with the developmental trajectory and lead to developing hypertension in adulthood. Prenatal hypoxia is often associated with intrauterine growth restriction that interferes with metabolism and can lead to multilevel changes. Therefore, we analysed the effects of prenatal hypoxia predominant...
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... of the described mechanisms as a response to prenatal hypoxia ensures sufficient blood flow to vital organs, such as the brain and heart, by peripheral vasoconstriction and reduction in oxygen consumption by the tissues and organs. We further describe the effects of prenatal hypoxia on cardiovascular regulatory mechanisms: the chemoreflex, adenosine, NO, ROS, and RAAS, as well as the effects of prenatal hypoxia on morphological-functional changes in the heart, blood vessels, and kidneys (Table 2). Evaluated resting ventilation and ventilatory response; periphery: reduced tyrosine hydroxylase activity within the first postnatal week and enhanced later; ...Context 2
... important regulatory mechanism responding to changes in the partial pressure of respiratory gases (oxygen and carbon dioxide) are peripheral chemoreceptors (Table 2). Acute prenatal hypoxia activates the carotid bodies and triggers a chemoreflex response [70]. ...Context 3
... lacking the A 1 receptor have more serious consequences after exposure to prenatal hypoxia, more pronounced growth restriction, and more significant morphological changes in the heart receptor mice, the expression of HIF-induced genes was up-regulated [83,111]. This points to an important link between the adenosine and HIF signalling pathways in the hypoxia in the prenatal period (Table 2). The importance of adenosine and its receptors in prenatal programming was reported in a study with non-selective adenosine antagonists. ...Context 4
... dilatation is caused by increased NO, adenosine, and prostanoids. In peripheral vessels, increased NO synthesis by endothelial NO synthase (eNOS) compensates for the vasoconstrictor responses of hypoxia (Table 2) through the actions of the chemoreflex and catecholamines [70]. The release of catecholamines is reduced by NO donors, and the inhibition of NO synthesis conversely increases the release of catecholamines from the adrenal medulla [70]. ...Context 5
... oxygen concentration leads within a few minutes to the suppression of anabolism, stimulation of anaerobic glycolysis, and inhibition of aerobic metabolism in mitochondria [109]. The importance of phenotypic reprogramming of mitochondria in the heart after an insult is known in adults and can also be important for the prenatal programming of heart disease in adulthood (Table 2) [90]. The significance of mitochondria function in cardiovascular programming is demonstrated by using MitoQ in the treatment of prenatal hypoxia [53,91,92]. ...Context 6
... development of fibrosis and cardiac hypertrophy in foetuses exposed to prenatal hypoxia can be amplified by increased salt intake, which only supports the role of RAAS in the development of these morphological changes [94]. Moreover, AT 1 and AT 2 receptors play a significant role in the prenatal programming of blood pressure and setting the set points of its regulatory mechanisms (Table 2) [33,94]. This conclusion is supported by using RAAS blockers, which reduce blood pressure and eliminate the effects caused by prenatal hypoxia in the cardiovascular system [118]. ...Similar publications
Abnormal placental angiogenesis is associated with the occurrence of intrauterine growth restriction (IUGR) in piglets, and effective treatment strategies against this occurrence remain to be explored. Adenosine has been reported to play an important role in angiogenesis, but its role in placental angiogenesis is still unknown. Here, we investigate...
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... The rats lived in typical vivarium settings, which included 20-25°C, 50-55% humidity, daylight, a feed that was appropriate for this species of laboratory animals, and unlimited access to water. The chronic hematic nitrite-induced PH model was employed in this study [17,18]. For a fixed term of pregnancy, mature male rats were placed with virgin female rats with a ratio of 2 males per 4 females. ...
... The Pregnancy period was counted starting from the discovery of spermatozoids in the vaginal smear (day 1 of the pregnancy). Modelling hematic hypoxia was performed in the prenatal period of development by daily intraperitoneal administration of sodium nitrite solution to pregnant female rats from day 16 to day 21 of the pregnancy at 50 mg/kg (the dose causing moderate hypoxia) [17]. Control pregnant rats received physiological solution in the same regime. ...
Many children and adults who have suffered prenatal hypoxia at an early age develop many serious diseases. This disease is an actual problem of pediatric cardiology and little studied. The aim was to analyze the cardioprotective effect of L-arginine, Thiotriazoline, Angioline and Mildronate on the cardiovascular system of rats after prenatal hypoxia. Methods: The experiments were carried out on 50 emale white rats; intraperitoneal sodium nitrite solution was administered daily to pregnant female rats after 16 days at a dose of 50 mg/kg. Control pregnant rats received saline. The offspring were divided into groups: 1 – intact; 2 – the control group of rat pups after PH, daily treated with physiological saline; 3 – 6 groups of rat pups after PH, treated daily from the 1st to the 30th day after birth. Heat shock protein HSP70 was determined by enzyme immunoassay, ST2 Nitrotyrosine, eNOS was observed by ELISA. Results: Angiolin showed a high cardioprotective effect even a month after discontinuation of the drug, and after introduction, the highest decrease in ST2, nitrotyrosine was revealed. Thiotriazoline and L-arginine have an antioxidant effect and a positive effect on eNOS expression. increased the concentration of HSP70. Mildronate increased the expression of eNOS and the concentration of HSP70 in the blood of experimental rats after a course of administration, but did not show an antioxidant effect and did not reduce the concentration of nitrotyrosine. The results obtained indicate the cardioprotective effect of modulators of the NO system with different mechanisms of action of drugs after experienced prenatal hypoxia.
... It is well-known that prenatal hypoxia is one of the most common pathologies of embryonic development, which has long-term negative health consequences throughout the subsequent life, including premature aging. Based on the analysis of the accumulated evidence, the review by Sutovska and co-authors [7] aims to emphasize the role of prenatal hypoxia in the formation of hypertension in adulthood. The authors convincingly conclude that even short-term prenatal hypoxia significantly affects the mechanisms of regulation of the cardiovascular system, programming the development of hypertension in adulthood. ...
Oxygen is one of the most important elements, ensuring the vital activity of the body [...]
... In recent years, animal models of prenatal hypoxia have been widely used to understand the molecular mechanisms of adverse outcomes in offspring. Prenatal hypoxia affects fetal growth and elicits many disturbances after birth including the development of the central nervous system and cardiovascular regulatory system (Peyronnet et al., 2000;Wang et al., 2021;Sutovska et al., 2022). Decreased oxygen supply and peripheral blood flow by gestational IH to the fetal organs such as the heart and brain have critical impacts on physiological functions of these organs (Baschat et al., 1997). ...
Gestational intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea that occurs frequently during pregnancy, and effects caused by this environmental change during pregnancy may be transmitted to the offspring. In this study, we aimed to clarify the effects of IH in pregnant rats on the skeletal muscle of adolescent offspring rats. Mother rats underwent IH from gestation day 7–21, and their 5-weeks-old male offspring were analyzed. All male offspring rats were born and raised under normoxia conditions. Although no general growth retardation was observed, we found that exposure to gestational IH reduces endurance running capacity of adolescent offspring rats. Both a respiratory muscle (diaphragm; DIA) and a limb muscle (tibialis anterior; TA) showed no histological abnormalities, including fiber size and fiber type distribution. To identify the possible mechanism underlying the reduced running capacity, regulatory factors associated with energy metabolism were analyzed in different parts of skeletal muscles. Compared with rats born under conditions of gestational normoxia, gestational IH offspring rats showed significantly lower expression of genes associated with glucose and lipid metabolism, and lower protein levels of phosphorylated AMPK and AKT. Furthermore, gene expression of adiponectin receptors one and two was significantly decreased in the DIA and TA muscles. In addition, the DIA muscle from adolescent rats had significantly decreased capillary density as a result of gestational IH. However, these changes were not observed in a sucking muscle (geniohyoid) and a masticating muscle (masseter) of these rats. These results suggest that respiratory and limb muscles are vulnerable to gestational IH, which induces altered energy metabolism with decreased aerobic motor function. These changes were partially owing to the decreased expression of adiponectin receptors and decreased capillary density in adolescent offspring rats.
... The circadian system develops "in utero" through exposure to maternal cues [20,21]. The importance of maternal-fetal communication is well known for other environmental factors such as nutrition, stress, and hypoxia, resulting in the development of diseases in adulthood [22]. The risk of maternal exposure to constant light during the second part of pregnancy has recently been underlined by the possibility that suppressed maternal melatonin can modify the epigenome of the fetal liver [23,24]. ...
... At P20 in the ALAN group, six pups from five mothers were used at each time point. At P20 in the CTRL group, we used six pups from five dams only during dark phase sampling (ZT14, 18,22); during the light phase, six pups from six dams at each time point were included. The pups were taken randomly from the home cage. ...
Artificial light at night (ALAN) is considered an environmental risk factor that can interfere with the circadian control of the endocrine system and metabolism. We studied the impact of ALAN during pregnancy on the hormonal and biochemical parameters in rat pups at postnatal (P) days P3, P10, and P20. Control dams (CTRL) were kept in a standard light-dark regime, and ALAN dams were exposed to dim ALAN (<2 lx) during the whole pregnancy. A plasma melatonin rhythm was found in all CTRL groups, whereas in ALAN pups, melatonin was not rhythmic at P3, and its amplitude was lowered at P10; no differences were found between groups at P20. Plasma corticosterone was rhythmic at P20 in both groups, with decreased mesor in ALAN pups. Plasma thyroid hormones exhibited an inconsistent developmental pattern, and vasopressin levels were suppressed at the beginning of the dark phase at P20 in ALAN compared to CTRL. Glucose and cholesterol showed significant daily rhythms in CTRL but not in ALAN offspring at P3. Exposure to ALAN during pregnancy disturbed the development of daily rhythms in measured hormones and metabolites, suggesting that ALAN during pregnancy can act as an endocrine disruptor that can interfere with the normal development of the progeny.
... The rats were kept under standard vivarium conditions at 20-25 С, humidity 50-55%, natural light, diet recommended for this species of laboratory animals, and water ad libitum. Here, we used the chronic hematic nitrite-induced PH model [11,12]. For a fixed term of pregnancy, mature male rats were placed with virgin female rats with a ratio of 2 males per 4 females. ...
... Our previous studies have obtained data indicating the role of the NO system in the formation of post hypoxic cardiomyopathy. So, in children who underwent intrauterine hypoxia, a deficiency of stable NO metabolites was found in blood against the background of eNOS inhibition [12]. ...
... Angiolin is able, together with vitamin C, to form L-carnitine and normalize the work of mitochondria [21]. In our work, it was found that angiolin normalized the amplitudes of the ventricular R wave and the amplitude of the repolarization T wave under conditions of myocardial ischemia, which is associated with an improvement in the energy supply of the myocardium and a more rational use of macroergs to ensure the contractile function of the heart [12]. Angiolin increases the expression of HSP 70 , which "prolongs" the action of HIF-1a, and also independently maintains the expression of NAD-MDH-mx, thereby maintaining the activity of the compensatory mechanism of ATP productionthe malate-aspartate shuttle mechanism for a long time. ...
Background. Posthypoxic cardiopathy is one of the risk factors for the development of cardiovascular pathology (rhythm disturbances, vascular dystonia, etc.) in subsequent age periods and requires the development of treatment approaches.
Objective. to evaluate the cardioprotective effect of modulators of the NO system by the effect on the ECG of rats after intrauterine hypoxia.
Methods. Modeling of prenatal hypoxia (PH) by daily intraperitoneal administration of sodium nitrite solution to pregnant female white rats weighing 220–240 g, aged 4.5 months, from the 16th to the 21st day of pregnancy at a dose of 50 mg/kg. The offspring were administered daily from the 1st to the 30th day of life – tiazotic acid (morpholinium 3-methyl-1,2,4-triazolyl-5-thioacetic acid), 50 mg/kg, angiolin ([S]-2,6-diaminohexane acid 3-methyl-1,2,4-triazolyl-5-thioacecate), 50 mg/kg, L-arginine, 200 mg/kg, meldonium (2-(2-carboxyethyl)-1,1,1-trimethylhydrazinium), 100 mg/kg. Аnd then after 2 months of life, an ECG was recorded using the ECG TUNNEL system (without anesthesia).
Results. Postponed PG leads to a decrease in heart rate and significant dominance of parasympathetic innervation in regulation of electrical activity of the heart, which can be caused by sinus blockade and may be a reflection of parasympathetic regulation of the heart instead of sympathetic control of electrical activity in the norm. The effectiveness of drugs can be presented in descending order: angiolin > tiazotic acid > meldonium. Angiolin proved to be more effective than tiazotic acidin normalizing the electrical activity of the heart and restoring the neurogenic regulation of the automatism of the function of the sinus node.
Сonclusions. The prospects of further study of modulators of the NO system with different mechanisms of action as means of cardioprotection of posthypoxic disorders of the cardiovascular system in newborns are experimentally substantiated.
Abstract: An important role in the network of interconnections between the mother and child is played by adipokines, which are adipose tissue hormones engaged in the regulation of metabolism. Alternations of maternal adipokines translate to the worsening of maternal insulin resistance as well as metabolic
stress, altered placenta functions, and fetal development, which finally contribute to long-term metabolic unfavorable conditions. This paper is the first to summarize the current state of knowledge concerning the concentrations of individual adipokines in different biological fluids of maternal and cord plasma, newborn/infant plasma, milk, and the placenta, where it highlights the impact of adverse perinatal risk factors, including gestational diabetes mellitus, preeclampsia, intrauterine growth restriction,
preterm delivery, and maternal obesity on the adipokine patterns in maternal–infant dyads. The importance of adipokine measurement and relationships in biological fluids during pregnancy and lactation is crucial for public health in the area of prevention of most diet-related metabolic diseases. The review highlights the huge knowledge gap in the field of hormones participating in the energy homeostasis and metabolic pathways during perinatal and postnatal periods in the mother–child dyad. An in-depth characterization is needed to confirm if the adverse outcomes of early developmental programming might be modulated via maternal lifestyle intervention.
Мета роботи: становити антигіпоксичні властивості фармацевтичної композиції на основі лівокарнітину. Матеріали та методи. Дослідження антигіпоксичних властивостей фармацевтичної композиції на основі лівокарнітину проведено на двох експериментальних моделях гострої гіпоксії, відтворених на нелінійних мишах-самцях (Mus musculus). Щоденно впродовж 15 діб та за годину до проведення тестів із визначення антигіпоксичної дії тваринам вводили ФК на основі лівокарнітину, а мишам групи позитивного контролю – референтний препарат – мексикор. Ефективність дії фармацевтичної композиції на основі лівокарнітину на експериментальних моделях гіпоксії визначено за показниками: коефіцієнт антигіпоксичної активності, середня тривалість життя тварин та відносна антигіпоксична активність. Результати й обговорення. Встановлено, що фармацевтична композиція на основі лівокарнітину в дозі 25 мг/кг на моделі гострої нормобаричної гіпоксії з гіперкапнією проявляє найбільшу антигіпоксичну активність, яка становить – 31 %, що відповідає активності препарату порівняння мексикор у дозі 16 мг/кг. На моделі гострої гемічної гіпоксії визначено більш виражену антигіпоксичну активність фармацевтичної композиції на основі лівокарнітину у дозі 25 мг/кг, яка становить 41 % та є дещо вищою порівняно із мексикором у дозі 16 мг/кг. Висновки. Визначено, що ФК на основі лівокарнітину у дозі 25 мг/кг при внутрішньошлунковому введенні мишам проявляє найбільш виражену антигіпоксичну дію на моделі гострої гемічної гіпоксії, порівняно із референс-препаратом мексикор у дозі 16 мг/кг (41 % проти 33 %). Профілактичне введення фармацевтичної композиції на основі лівокарнітину у дозі 25 мг/кг підвищує стійкість тварин до гіпоксичних станів. Встановлено виражену антигіпоксичну активність фармацевтичної композиції на основі лівокарнітину на моделі гострої гемічної гіпоксії, що зумовлює перспективність подальших фармакологічних досліджень для застосування в медичній практиці з метою профілактики наслідків фетоплацентарної недостатності.
