[Ratio of cations in hemolymph, blood serum of aquatic and terrestrial organisms].

A wide range of differences of cations concentrations (Na, K, Ca, Mg) in hemolymph, blood serum of multicellular animals and humans was revealed. It was established that constancy of K/Na ratio 0.034 +/- 0.001 is strictly maintained in these organisms. Except for some freshwater and marine organisms, Mg/Na ratio is sustained on the same level in the wide range of concentrations of these ions in serum of vertebrates and hemolymph of invertebrates. Ca/Na ratio is higher in hemolymph of freshwater mollusks. The question about possible reasons of physiological differences of Ca/Na and Mg/Na rations compared to constancy of K/Na ratio is discussed.

[Exenatide stimulated solute-free water excretion by human kidney].

Exenatide effect was studied in 55 human including 38 patients with type 2 diabetes mellitus without signs of diabetic nephropathy and primary renal diseases. Preliminary study with water load in volume from 0.5 to 1% b.w. showed that water load equal to 0.7% b.w. caused significant increase in urine excretion. The rise of diuresis after 10 microg Byetta (exenatide) injection and simultaneous water load of 0.7% of b.w. depended on increase in solute-free water clearance. Thus, exenatide (mimetic of GLP-1) action let us to consider its possible role as component of osmoregulation system in human. This peptide provides high efficiency of renal function in osmotic homeostasis.

[K+/Na+ in the animal extracellular fluid at weathering of granitoids and problem of the origin of life].

Leaching of granitoids of the paleoproterozoic age was performed from several seconds to 360 days in water solutions (pH < 6.0) in the oxygen or argon medium. Under these conditions the entrance of K+ into the solution has been shown to occur at the higher rate than that of Na+. The obtained data are considered as evidence in favor of a possibility of the existence at the earlier stages of the Earth geologic history of water reservoirs with predominance of K+ over Na+. The K+/Na+ ratio exceeding 1 has been shown in prokaryotes, in cells and tissues of the free living and parasitic species of invertebrate and vertebrate animals. At the same time in the extracellular fluid of the fresh water, marine, and terrestrial animals, in which the Na+ concentration varies from 13 to 482 mmol/l, the K+/Na+ ratio is preserved at the level of 0.034 +/- 0.001. These results are discussed in connection with the problem of origin of protocells and of concentration ratios of monovalent cations in water phases of multicellular organisms.

[Diet and water-salt balance in rats].

We compared parameters of water-salt balance in Wistar female rats fed normal chows during more than 2 weeks. Potassium content was 1.4-fold higher in diet I than in diet II, and sodium end water content was 3.3- and 7.5-fold higher in diet II than in diet I. Blood osmolality and concentration of Na+, K+, Mg2+ were equal in rats fed different chow. In water-loaded rats (5 ml of water/100 bw per os) fed different chow, urine flow rate did not differ, but solute-free water excretion was higher by 40.2% in the rats fed diet II vs. diet I. The sort of diet did not affect the renal sodium excretion during oral administration of 5 ml 0.9% NaCl per 100 g bw to rats. After vasopressin injection solute-free water reabsorption was 1.5-fold higher in rats fed diet II. Natriuretic and hydruretic effect of exenatide, glucagon-like peptide 1 mimetic, was weaker in rats fed diet I. The data obtained indicate that organism can effectively maintain blood parameters. The modulation of hormone regulatory effects on water and sodium balance was found to depend on the state of organism under diet consumed continuously.

[Natriuretic effect of exenatide: high efficacy and site of action].

Exenatide injection to female Wistar rats induced an increase in diuresis, urinary sodium and mild potassium excretion. The maximum natriuretic effect of exenatide was 18500 times more pronounced compared to that of furosemide in equimolar dose. The natriuretic and diuretic effects after combined administration of maximum doses of exenatide and furosemide were additive, which was indicative of different mechanisms of their action on the nephron. Exenatide probably inhibits sodium reabsorption in renal proximal segment. The data obtained might be essential for assessment of the clinical use of exenatide to excrete extracellular fluid excess in cases of edemation and to maintain potassium balance.

[Incretin role in osmotic homeostasis in rats].

Solute-free water clearance increased by 186% in water loaded rats treated with glucagon-like peptide 1 compared to untreated group. The effect of glucagon-like peptide 1 was reproduced in experiments with its synthetic analogue exenatide. Serum osmolality in water loaded rats treated with exenatide was closer to normal level on 30, 45, 60 min of experiment compared to the untreated group and reached the control value in 60 min. Administration of glucagon-like peptide 1 receptor antagonist to water loaded rats delayed (5 ml per 100 g bw) or prevented (2 ml per 100 g bw) increase in solute-free water clearance. The obtained data suggest the involvement of glucagon-like peptide 1 in osmotic homeostasis and indicate the unique physiologic role of incretins in regulation of water balance.

[Synthesis and investigation of effects of conopressin S analogues on ion and water excretion by rat kidney].

The investigation deals with effect of analogues of conopressin S--a peptide of the vasopressin family with amino acid replacement in the 2nd and 4th positions (characteristic of invertebrate peptides)--on transport of water and ions in the rat kidney. At administration to female Wistar rats, 1-deamino-conopressin S produced a weak action on water transport and had no effect on urinary K+ and Na+ excretion. Its analogue, 1-deamino-Tyr2-conopressin S, caused antidiuretic and kaliuretic action without affecting the Na+ excretion. Estimation of significance of the variant of optic isomer of arginine in the 4th and 8th position of the molecular for the antidiuretic and kaliuretic action of the peptide showed that 1-deamino-Tyr2,D-Arg4-conopressin S and 1-deamino-Tyr2,D-Arg4,8-conopressin S did not affect the urinary K+ excretion and renal water reabsorption, whereas action of 1-deamino-Tyr2,D-Arg8-conopressin S did not differ from action of 1-deamino-Tyr2-conopressin S. Thus, it has been established that the selective kaliuretic action of analogues of conopressin S on rat kidney depends on the presence of tyrosine in the 2nd and of L-arginine, but not of D-arginine, in the 4th position of the molecule.

[Quantum processes in evolution of regulation of living system (mathematical modelling)].

We have developed an imitation model of the appearance of regulation of physiological functions of protocell at the initial stages of evolution of living system. It is based on suggestion of the appearance of signal function in spontaneously formed products of partial hydrolysis of the protocell polypeptides, based on which there appear the regulatory molecules--quanta of regulation. For construction of the model, the mathematical apparatus of final automats and of genetic algorithm is used. The model has demonstrated the positive role of involvement of regulatory peptides in the system of regulation of protocell functions to provide its viability under the changing envelopment conditions.

[Comparison of reabsorption of osmotically free water in the bud and energy of interaction of vasotocin analogs with a V2-receptor].

The calculated values of the binding energy of nonapeptides with receptors in docking with their influence on reabsorption of osmotically free water in a rat bud in vivo were compared. Vasotocin and some its analogs were intramuscularly introduced to non-narcotized rat females of the Wistar line in doses from 0.1 pmol to 0.5 nmol/kg of body weight against the background of peroral water load (50 ml/kg of body weight). A significant correlation between the calculated interaction energy of peptides with V2-receptors and an increase of reabsorption of osmotically free water in the rat bud stimulated by injection of nonapeptides was found. The results evidence that alterations in rat bud in vivo caused by analogs of vasotocin and their interactions with V2-receptors can be accurately simulated.

[Physiological analysis of various types of osmotic diuresis].

Efficacy of drugs reduced proximal reabsorption was compared in experiments with female Wistar rats. Urine flow rate for the 1st h of experiment was enhanced after polyethylene glycol-400 (PEG) and 6% Na2SO4 infusion by over 30-fold, exenatide--40-fold, glycerol--11-fold as compared with the control. The maximal values of Na+ excretion were observed during Na2SO4 and exenatide administration (280 +/- 31 micromol/h vs. 3.2 +/- 0.6 Imol/h/100 g bw). The highest K+ excretion was revealed in experiments with glycerol administration (41 +/- 5 micromol/h vs. 7 +/- 2 micromol/h/100 g bw), Mg2+ --after exenatide injection (5.3 +/- 1.3 micromol/h vs. 0.16 +/- 0.03 micromol/ h/100 g bw). Diuretic effects were additive after combined administration of maximal doses of exenatide and PEG which suggests a different mechanism of action of solutes filtrated (PEG) to the proximal nephron segment and generated due to Na+/HW-exchange inhibition (exenatide). Osmotic diuretics differ by potency, mechanism of diuretic action and selectivity of ion excretion).

[S.S. Yudin. To the 120th anniversary of birth].

In October, 2011 120 years from the birth day of the great surgeon acad. USSR Ac. Med. Sci. S.S. Judin. Article include data on S.S.Judin's work and his life in Novosibirsk, new materials of the biography of the great surgeon, original photos.

[Human physiology: kidney].

The content of human physiology as an independent part of current physiology is discussed. Substantiated is the point that subjects of human physiology are not only special sections of physiology where functions are inherent only in human (physiology of intellectual activity, speech, labor, sport), but also in peculiarities of functions, specificity of regulation of each of physiological systems. By the example of physiology of kidney and water-salt balance there are shown borders of norm, peculiarities of regulation in human, new chapters of renal physiology which have appeared in connection with achievements of molecular physiology.

[Incretory function of the kidney].

Participation of kidney in maintenance of constancy of parameters of the organism internal medium is connected with formation in it of physiologically active substances. They are components of systems of regulation of water-salt balance, arterial pressure, blood coagulation, erythropoiesis. Mechanisms of normalization by kidney of concentration of hormones in blood and of modulation of action of hormones are analyzed.

[Diabetes mellitus: renal osmoregulating function].

AIM: To evaluate the kidney status from osmotic urine concentration in different stages of diabetes mellitus (DM) to define whether not only glomeruli and proximal tubules, but also renal medullary substance structures are involved into the pathological process, as well as their reaction to endogenous vasopressin production. SUBJECTS AND METHODS: Forty patients with a 1-to-28-year history of DM, including 18 with diabetic nephropathy, 10 with chronic renal failure, and 22 without diabetic nephropathy, were examined. Urine and blood osmolality were determined and renal osmoregulating function was estimated. RESULTS: Decreased glomerular filtration rate was found in relation to the duration of DM. The osmolality of nocturnal urine samples tended to diminish during short-term deprivation depending on the duration of DM. Increased diuresis in DM was shown to correlate with the higher reabsorption of osmotically free water. CONCLUSION: Diminished renal concentrating capacity in DM appears to depend on evolving renal failure rather than vasopressin resistance. The application of a new approach, by calculating the clearance of sodium-free water, suggests that its increased reabsorption favors normalization of serum osmolality in hyperglycemia.

[Similarity of natriuretic action and qualitative differences of the hydrouretic action of 1-deamino-arginine-vasotocin and furosemide in rats].

Injections of furosemide at a dose of 0.3 micromol per 100 g body weight or 1-deamino-arginine-vasotocin (1dAVT) at a dose of 0.05 nmol per 100 g body weight induced nearly equal increase in urinary sodium excretion: up to 406 +/- 20 and 405 +/- 23 micromol/2 h, respectively. Increase in urinary sodium excretion after injection of 1d-AVT was followed by enhancement of solute free water reabsorption from -0.51 +/- 0.05 to -2.75 +/- 0.11 ml/2 h (p < 0.05). On the contrary, furosemide injection induced a significant decrease in solute free water reabsorption to -0.19 +/- 0.06 ml/2 h (p < 0.05) and led to the appearance of solute free water in urine during peak of diuretic reaction. These data for the first time show that furosemide not only decreases sodium reabsorption, but also blocks some componentin molecular mechanism of vasopressin-dependent increase of the osmotic permeability of water.

[From quantum to integrative physiology].

Physiology studies the functions of different organs, systems and how they maintain the integrity of organisms. Nervous and endocrine systems react to stimulus, causality plays a key role in their activities. Physical and chemical conditions of fluids in the internal environment serve as a background and an active modulator for regulatory influences. Autacoid formation is in many respects based on probable events. It has been proved, that during the formation of regulatory systems in cell evolution the appearance of regulatory molecules was based on statistical probability of quantum events: sporadical appearance in cells during metabolism of peptides, lipids, hydrolysis of larger molecules on fragments, quanta, which received physiological activity in the form of function regulators. These processes in their adapted, according to Darwin's mechanism of natural selection, value were recorded into the genome since synthesis readings of the polypeptides were fixed. The formation of multicellular organisms was promoted by the arise of regulatory systems and their integration under the supervision of the nervous system.

[Influence of new neurohypophyseal hormone analogs on sodium and water reabsorption in rat kidney].

New analogs of some neurohypophyseal hormones (oxypressin, hydrin, glumitocin, vasotocin) have been synthesized. Experiments with injection of these peptides to rats showed that substitution of C-terminal glycinamide on beta-ethanolamine (glycinol) or ethylamine in 1-deamino-arginine vasotocin resulted in loss of natriuretic but not antidiuretic activity. Analogs of oxypressin and hydrin exhibited neither natriuretic activity nor ability to affect water reabsorption. Glumitocin analog induced renal sodium ion excretion and did not influence potassium ion excretion.