Endogenous multiple modified LDL (mLDL) and the renin-angiotensin system play a significant role in the development of atherosclerosis. It has been found that by behavioral and hemodynamic parameters the physiological activity of angiotensin II (Ang II) in combination with mLDL is considerably modified due to weakening of its diuretic effect and the inversion of hypertensive and tachyarrhythmic effects. Atherosclerosis is a long-term pathological process, so a single administration of artificially synthesized Ang I-mLDL complexes can be considered a model of the first contact of the body with pathogenic factors. We believe that angiotensin complexes with mLDL participate in adaptive and compensatory mechanisms at the initial stages of atherosclerosis and later contribute to its progression.

In rats with acute hypo- and hyperglycemia the initial effects of free angiotensin IV and its complexes with functionally different carrier proteins (transport protein BSA, neuron-specific protein S100b) on hemodynamics and behavior of rats were qualitatively altered, in comparison with those in intact animals. At the same time, free angiotensin IV under conditions of hypo- and hyperglycemia paradoxically acquired functions of angiotensin II (moderate hypertension, tachycardia, polydipsia and activation of instrumental drinking behavior). Concurrently, complexes of angiotensin IV with BSA and S100b acquired functions of free angiotensin IV (hypotensia, suppression of drinking behavior). It is suggested that complexes of angiotensin IV with functionally different proteins are involved in a differentiated way first in compensation of behavior and hemodynamics impairment produced by acute and/or chronic hypo- and hyperglycemia, and then in qualitative transformation of these adaptive processes into stable pathological condition involving mechanisms of so called “metabolic memory”.

Experimental hypoglycemia and hyperglycemia eliminated the differences in the regulatory functions of free angiotensin II and its complexes with carrier proteins (transport protein BSA and neurospecific protein S100b) in rats. Under these conditions, free and protein-bound angiotensin II primarily suppressed operant drinking behavior and reduced the hypertensive and tachyarrhythmic effects in comparison with control rats. These changes were most pronounced during acute hyperglycemia. We hypothesized that complexes of angiotensin II with functionally different proteins are differentially and simultaneously involved in not only compensation of behavioral and hemodynamic disturbances during acute and/or chronic hypoglycemia and hyperglycemia, but also their transformation into pathological processes mediated by the socalled metabolic memory mechanisms.

A method for determining atherogenicity of the immune complexes containing multiple modified low-density lipoprotein (mmLDL) in complement fixation test has been found. In the proposed method, the precipitate immune complexes containing mmLDL (IC mmLDL) was prepared from human serum by treating it with buffer (8.3% of th PEG 3350 and 3.3% PVP 12600 th in the ratio 1: 1.2) for 10 min at 23 °C. IC mmLDL aggregates were separated by centrifugation at 3100g for 10 min at 23 °C. The precipitate IC mmLDL was dissolved in buffer without PEG and PVP, cholesterol content and the degree of binding of guinea pig complement were measured. Atherogenicity of the IC mmLDL was registered as the ratio of the degree of complement binding to cholesterol in the the immune complexes.

Changes in blood glucose levels are paralleled by modification of normal activities of angiotensin II and angiotensin IV. Hypo- and hyperglycemia similarly reduced the hypertensive effect of angiotensin II and similarly distorted the initial hypotensive effect of angiotensin IV. Presumably, the adaptation and compensatory processes in the renin-angiotensin system under conditions of shifted homeostatic constants manifest by phenomena of external reintegration and redistribution of functions of its individual peptide components. This provides restructuring of the mechanisms of intra- and intersystemic organization of physiological functions under extreme conditions.

The parameters of heart rate variations were examined in emergency care doctors that demonstrated the initial signs of defensive psychological burnout syndrome related to their professional activity. These parameters were compared within each of two groups with different individual typological features. The differences in the heart rate variability parameters were revealed between the examinees that were at the compensation or alarm stages of the burnout syndrome.

We compared physiological activity of synthetic analogues of endogenous protein-peptide compounds, complexes of angiotensin II1-7 with functionally different proteins (transport protein, serum albumin; and neurospecifi c Ca2+-binding protein, S100b). Physiological activity of angiotensin II1-7 was shown to depend on the type of a carrier protein. Our results suggest that complexes of angiotensins with BSA and S100b are strong factors for the integration of central and peripheral functions at the homeostatic and behavioral level.

Systemic administration of angiotensin II was followed by an increase in systolic BP and HR in rats with carotid glomectomy, the time of attaining maximum values in treated animals was much higher than in sham-operated controls. Injection of angiotensin IV slightly reduced systolic BP in sham-operated animals and increased it in rats with carotid glomectomy. The involvement of the local renin-angiotensin system of the carotid body in systemic mechanisms of hemodynamics regulation is discussed.

We compared physiological activity of synthetic complexes from angiotensin IV and functionally different proteins (transport protein, bovine serum albumin; and neurospecific Ca(2+)-binding protein, S100b) as model analogues of endogenous protein-peptide complexes. Physiological activity of angiotensin IV was specifically modified by these proteins. Our results suggest that complexes of angiotensin IV with bovine serum albumin and S100b are strong factors for the integration of central and peripheral functions at the homeostatic and behavioral level.

We compared activity of synthetic complexes of angiotensin II and functionally different proteins (transport protein, serum albumin and neurospecific Ca 2+ -binding protein S100b) as analogues of endogenous protein-peptide complexes. Physiological activity of angiotensin II was specifically modified by these proteins. It was hypothesized that the complex of angiotensin II and S100b is primarily involved in the regulation of hemodynamics, whereas the complex of angiotensin II and bovine serum albumin plays a role in the formation and realization of drinking behavior.

We report here a comparative analysis of the involvement of a number of components of the renin-angiotensin system in the performance of simple and complex forms of drinking behavior and thirst-associated non-drinking types of behavior. On central (intracerebroventricular) microinjection, [des-Asp 1 ]-angiotensin I at doses equieffective to those of angiotensins II and III was found to be involved only in the performance of simple (taking water from the bowl) and linked forms of activity (comfort behavior, stress grooming, orientational-investigative, and feeding behavior). Angiotensin II was involved in the central mechanisms of complex acquired drinking behavior, selectively modulating its key stages (initial, final), while angiotensin III was involved only in the mechanisms of reproduction of the complex skill. All three substances induced “innate patterns of behavior” specific for each compound, these occurring at fixed periods of time after intracerebral microinjection. The effects of these substances were selectively suppressed by the AT1 receptor blocker losartan potassium.

The comparative analysis of physiological activity of ((chimeric)) complexes angiotensin-II and beta-endorphin with proteins and native peptides was performed Some behavioral and physiological responses after active immunization by conjugates angiotensin-H and beta-endorphin with proteins were obtained. It's suggested that ((chimeric)) forms of regulatory peptides play a specific informational role in systemic organization of behavior. An important function of this substances due to it's conformational properties and it's participation in hierarchical organization of integrative processes in nervous system is discussed.

: Central mechanisms of angiotensin involvement in initiation and realization of operant forms of drinking behavior were investigated. It was suggested that intracerebroventricular microinjection of angiotensin-II and angiotensin-IIl specifically affected the learned forms of drinking behavior. The experiments demonstrated that [des-Asp1]-angiotensin-I produced only the natural forms of drinking behavior. Angiotensins modulated specific forms of thirst-associated behavior such as exploring, grooming, and ingestive behavior. Injections of AT1 receptor antagonist losartan were associated with acute water intake decrease and sharp operant behavior inactivation.

Systemic administration of angiotensin II after carotid glomectomy produced a less pronounced dipsogenic effects (consumption of water and NaCl solution) compared to sham-operated control animals. Injection of angiotensin II into the lateral cerebral ventricles of the same glomectomized rats increased water and NaCl consumption to a level surpassing that of sham-operated animals. The number of drinking acts and comfortable grooming acts decreased in glomectomized animals after systemic administration of angiotensin II, but increased after its intracerebral injection compared to the control. The results confirm the hypothesis that carotid chemoreceptors, as the peripheral component of the renin-angiotensin system, participate in the mechanisms of angiotensin-induced thirst, "salt appetite", and associated behavioral forms (comfortable grooming) synergically with the central cerebral receptors.

The paper presents some new data and original approaches to study of the role of opioid and vasoactive peptides in the integrative functioning of the brain. The authors performed a comparative analysis of the physiological activity of native and complex (combined with protein) forms of these biologically active substances, and discuss a possible role of autoimmune processes in peptide self-regulation of goal-directed behavior.

Carotid glomectomy in rats reduced daily water consumption and increased daily consumption of NaCl solution. Sham operation did not modify water and salt consumption. Intraperitoneal injection of angiotensin-II did not stimulate drinking motivation in the majority of rats subjected to carotid glomectomy. Injection of angiotensin-II to sham-operated and intact animals induced active consumption of both fluids during one hour. These results attest to the involvement of the carotid body in the regulation of consumption of water and sodium ions (the main elements of osmotic blood pressure) and the involvement of angiotensin-sensitive receptors of carotid body cells in the formation of thirst and salt appetite motivation, regulated by the renin-angiotensin system.

The effects of angiotensin-II, angiotensin-III, and [des-Asp1-angiotensin-I on drinking and attendant behaviors of rats were studied. Special behavioral patterns were observed after intracerebroventricular administration of angiotensins. The nature and possible mechanisms of behavioral effects of peptidergic brain stimulation are discussed.

A comparative analysis of the physiological actions of native angiotensin I and angiotensin II and protein-peptide complexes of angiotensin I and angiotensin II on drinking behavior in rats was performed. The protein-peptide complexes of angiotensin I and angiotensin II had wider spectra of physiological activity than the native peptides. Protein-conjugated angiotensin I, unlike the motivationally neutral native angiotensin I, produced marked activation of innate drinking behavior in mice. The protein-peptide complex of angiotensin II showed selective effects on acquired drinking behavior. These data are assessed with respect to the specific involvement of protein-peptide complexes of angiotensin I and angiotensin II in the mechanisms of thirst motivation during the performance of innate and acquired habits.

Protein-peptide complexes involved in learned and natural drinking behavioral patterns were comparatively analyzed in rats. Active immunization with protein-conjugated angiotensin II and beta-endorphin produces some behavioral responses. It is suggested that protein complexes of these peptides play a specific informational role in the systemic organization of learned behavior. The paper discusses whether these complexes perform an important function due to their conformational properties and their participation in the hierarchical organization of integrative processes in the nervous system.

The system architectonics of "systemoquanta" of rat drinking behavior was objectively evaluated in the dynamic process of its formation by means of studying intermediate and final results. The developed experimental equipment made it possible to determine characteristic features of formation and realization of drinking "systemoquanta" and the dynamics of their internal structure. Various "strategies" of system organization of identical behavior were revealed in rats of different groups. The revealed peculiarities of the internal structure of "systemoquanta" in rats of different groups are probably determined by the innate individual differences in the processes of prediction and estimation of intermediate and final results in the framework of strategic "systemoquantum" of drinking behavior.