An anthropogenic model of cardiovascular system adaptation to the Earth's gravity as the conceptual basis of pathological anthropology.

Applying human biological evolution to solve topical problems of medicine and preventive cardiology was inspired by the realization of the need for clinical and experimental studies of biological (evolutionary) prerequisites in the occurrence of a pathology. Although it has been stated that there is a need to provide a full biological understanding of features, including those that increase an animal's vulnerability to diseases, unfortunately, in this regard, erectile and associated adaptations to the Earth's gravity in their physiological and pathological manifestations have not been considered. At the same time, it should be noted that humans, unlike other animal species, have the greatest vulnerability of the cardiovascular system (CVS). The latter is associated with fundamental differences in the functioning and regulation of the CVS by the influence of gravity on blood circulation in humans as upright creatures. Based on a review of comparative physiological, ontogenetic, and clinical studies from an evolutionary perspective, the idea of adaptation to the Earth's gravity when walking upright in humans is justified as an anthropogenic basis for the physiology and pathology of the cardiovascular system and hemodynamic support systems (physio-anthropology and pathological anthropology).

The role of oxytocin and vasopressin in the pathophysiology of heart failure in pregnancy and in fetal and neonatal life.

Pregnancy and early life create specific psychosomatic challenges for the mother and child, such as changes in hemodynamics, resetting of the water-electrolyte balance, hypoxia, pain, and stress, that all play an important role in the regulation of the release of oxytocin and vasopressin. Both of these hormones regulate the water-electrolyte balance and cardiovascular functions, maturation of the cardiovascular system, and cardiovascular responses to stress. These aspects may be of particular importance in a state of emergency, such as hypertension in the mother or severe heart failure in the child. In this review, we draw attention to a broad spectrum of actions exerted by oxytocin and vasopressin in the pregnant mother and the offspring during early life. To this end, we discuss the following topics: 1) regulation of the secretion of oxytocin and vasopressin and expression of their receptors in the pregnant mother and child, 2) direct and indirect effects of oxytocin and vasopressin on the cardiovascular system in the healthy mother and fetus, and 3) positive and negative consequences of altered secretion of oxytocin and vasopressin in the mother with cardiovascular pathology and in the progeny with heart failure. The present survey provides evidence that moderate stimulation of the oxytocin and vasopressin receptors plays a beneficial role in the healthy pregnant mother and fetus; however, under pathophysiological conditions the inappropriate action of these hormones exerts several negative effects on the cardiovascular system of the mother and progeny and may potentially contribute to the pathophysiology of heart failure in early life.

Impaired hypotensive effects of centrally acting oxytocin in SHR and WKY rats exposed to chronic mild stress.

The present study was designed to determine the role of centrally acting oxytocin (OT) in the regulation of blood pressure during chronic mild stress (CMS) in spontaneously hypertensive (SHR; n = 36) and normotensive Wistar-Kyoto (WKY; n = 38) rats. The rats were implanted with osmotic minipumps for intracerebroventricular infusions of 0.9% NaCl, OT, and oxytocin receptor antagonist (OTANT) and divided into two groups: SHR and WKY 1) exposed to 4-wk CMS and 2) not exposed to stress (controls). After 4 wk, hemodynamic parameters were recorded at rest and after an application of acute stressor [air-jet stress (AJS)]. Resting mean arterial blood pressure (MAP) was significantly lower in CMS-exposed SHR and WKY infused with OT than in the corresponding groups receiving saline. Exposure to CMS exaggerated the AJS-dependent pressor response in WKY receiving saline but not in the corresponding group of SHR. OT infusion reduced the AJS-dependent pressor response in both CMS-exposed and not exposed SHR and in CMS-exposed WKY. Intracerebroventricular infusion of OTANT potentiated the AJS-dependent pressor response in both stressed and not stressed WKY rats but not in SHR. The results show that centrally delivered OT decreases resting MAP during CMS in both SHR and WKY rats and that in SHR it reduces pressor responses to AJS under control and CMS conditions, whereas in WKY this effect is significant only after CMS exposure. The study indicates that endogenous centrally acting OT may play an essential role in buffering pressor responses to AJS in CMS-exposed and not exposed WKY rats and that this function is significantly impaired in SHR.

The effect of blockade of the central V1 vasopressin receptors on anhedonia in chronically stressed infarcted and non-infarcted rats.

Chronic mild stress (CMS) and myocardial infarction (MI) induce anhedonia, which is one of the symptoms of depression. The purpose of this study was to determine the role of the central V1 vasopressin receptors (V1R) in post-CMS and post-MI anhedonia. To this end, we investigated the effect of blockage the central V1R [28days of intracerebroventricular (ICV) infusion of V1 receptors antagonist (V1RANT)] on CMS-induced and the post-infarct anhedonia. The experiments were conducted on conscious MI or sham-operated (SO) rats that were either exposed to CMS for 20days or remained at rest. The sucrose/water intake ratio (S/W) was measured to determine hedonic behavior. Seven days after MI, the S/W was reduced. This effect was no longer present 37days after the infarction and was also absent in the SO rats. Exposure to CMS reduced the S/W in SO rats also. In the CMS-exposed MI rats, the S/W was similar to that in the CMS-exposed SO rats. ICV administration of V1RANT abolished reductions in the S/W in the CMS-exposed MI rats, however, it did not influence S/W in the SO rats exposed to CMS and in the MI and SO rats not exposed to CMS. We conclude that: (1) myocardial infarction and chronic stressing cause anhedonia, (2) myocardial infarction-induced anhedonia appears to be transient, (3) myocardial infarction does not potentiate CMS-induced anhedonia, and (4) CMS-induced anhedonia critically depends on the stimulation of the central V1 receptors.

Oxytocin differently regulates pressor responses to stress in WKY and SHR rats: the role of central oxytocin and V1a receptors.

The role of central oxytocin in the regulation of cardiovascular parameters under resting conditions and during acute stress was investigated in male normotensive Wistar-Kyoto (WKY; n = 40) and spontaneously hypertensive rats (SHR; n = 28). In Experiment 1, mean arterial blood pressure (MABP) and heart rate (HR) were recorded in WKY and SHR rats at rest and after an air-jet stressor during intracerebroventricular (ICV) infusions of vehicle, oxytocin or oxytocin receptor (OTR) antagonist. In Experiment 2, the effects of vehicle, oxytocin and OTR antagonist were determined in WKY rats after prior administration of a V1a vasopressin receptor (V1aR) antagonist. Resting MABP and HR were not affected by any of the ICV infusions either in WKY or in SHR rats. In control experiments (vehicle), the pressor response to stress was significantly higher in SHR. Oxytocin enhanced the pressor response to stress in the WKY rats but reduced it in SHR. During V1aR blockade, oxytocin infusion entirely abolished the pressor response to stress in WKY rats. Combined blockade of V1aR and OTR elicited a significantly greater MABP response to stress than infusion of V1a antagonist and vehicle. This study reveals significant differences in the regulation of blood pressure in WKY and SHR rats during alarming stress. Specifically, the augmentation of the pressor response to stress by exogenous oxytocin in WKY rats is caused by its interaction with V1aR, and endogenous oxytocin regulates the magnitude of the pressor response to stress in WKY rats by simultaneous interaction with OTR and V1aR.

Oxytocin in the cardiovascular responses to stress.

The present study was designed to determine the role of central oxytocin (OXY) in regulation of the cardiovascular responses to the alarming stress. Three groups of male, normotensive Sprague Dawley rats, received intracerebroventricular (i.c.v.) infusion of one of the following: 1) vehicle, 2) OXY or 3) OXY antagonist (OXANT). Mean arterial blood pressure (MABP) and heart rate (HR) were recorded at rest, during and after application of the alarming stressor (air jet). Under resting conditions the i.c.v. infusions of vehicle, OXY or OXYANT did not influence the cardiovascular parameters. The alarming stressor evoked significant increases in MABP and HR that were significantly greater in the rats receiving i.c.v. infusion of oxytocin antagonist than in those receiving vehicle or OXY. The study provides evidence that stimulation of the brain oxytocin receptors by endogenous oxytocin plays significant role in inhibition of cardiovascular responses to stress.

Fluid consumption, electrolyte excretion and heart remodeling in rats with myocardial infarct maintained on regular and high sodium intake.

The purpose of the study was to determine effect of high sodium intake on fluid and electrolyte turnover and heart remodeling in the cardiac failure elicited by myocardial infarction (MI). The experiments were performed on four groups of Sprague Dawley rats maintained on food containing 0.45% NaCl and drinking either water (groups 1, 2) or 1% NaCl (groups 3, 4). Groups 1 and 3 were sham-operated while in groups 2 and 4 MI was produced by the coronary artery ligation. In each group food and fluid as well as sodium intake, urine (Vu), sodium (UNaV), potassium (UKV) and solutes (UosmV) excretion were determined before and four weeks after the surgery. Size of the infarct, left ventricle (LV) weight and diameter of LV and right ventricle (RV) myocytes were determined during post-mortem examination. Before the surgery groups 3 and 4 ingested significantly more fluid and sodium, had higher Vu, UNaV, UKV and UosmV than the respective groups 1 and 2. In groups 2 and 4 MI resulted in significant decrease in Vu, UNaV and UosmV in comparison to the pre-surgical level. In Group 4 MI resulted also in a significant decrease of food and sodium intake. The MI size did not differ in groups 2 and 4 while diameter of LV myocytes was significantly greater in groups 2 and 4 than in groups 1 and 3, and in group 4 than in group 2. The study reveals that prolonged high sodium consumption increases fluid and electrolyte turnover both in the sham and in the MI rats and that the MI causes decrease in food and sodium intake in rats on high but not on regular sodium intake. In addition high sodium diet promotes development of greater post-MI hypertrophy of the LV myocytes.