[Interaction of renin-angiotensin system inhibitors with dopamine in rat kidney].

Dopamine (1 mg/kg, s.c.) causes 2.2-fold increase in diuresis (p < 0.05) in anesthetized rats, which is accompanied by an increase in the urinary excretion of sodium and potassium by a factor of 2.2 and 2.8, respectively (p < 0.05). Preliminary administration of the ACE inhibitor enalapril (1 mg/kg, p.o., for 7 days) enhances the renal dopamine response with 3.5-fold increase in its diuretic effect and increases natriuresis 3.2 times and urine potassium excretion 5 times (p < 0.05). After preliminary introduction of the AT1-angiotensin receptor antagonist losartan (1 mg/kg, p.o., for 7 days) dopamine causes 3.3-fold increase in diuresis, 3.1-fold increase in natriuresis, and 3-fold increase in kaliuresis (p < 0.05). Preliminary administration of the direct renin inhibitor aliskiren (4 mg/kg, p.o., for 7 days) is accompanied by 6-fold increase in the diuretic effect of dopamine and increases natriuresis 7.2 times and urine potassium excretion 7 times (p < 0.05). It is concluded that renin-angiotensin system (RAS) of renal tissues is involved in the mechanism of dopamine action in the kidney, acting as a modulator that prevents excessive loss of water and electrolytes with urine.

[Nephroprotective properties of third-generation beta-adrenoblockers].

Experimental and clinical data on the nephroprotector properties of third-generation beta-adrenoblockers nebivolol and carvedilol are reviewed. These properties are related to the antihypertensive effect and ability of drugs to suppress oxidative stress in glomerules, proximal renal tubules, and surrounding interstitial tissue.

[Analysis of the role of neurohumoral systems in action of dopaminomimetic dopamine on ion-regulating renal function].

Dopamine causes in anesthetized rats expressed diuretic response that is accompanied by an increase in GRF and a significant enhance of sodium and potassium excretion. Pretreatment the animals in diclofenac sodium or contrical in doses, that inhibit respectively activity of renal PG-system and kallikrein-kinin system, don't prevent of renal effects of dopamine. Preliminary assignment a direct renin inhibitor aliskiren enhances the diuretic, natriuretic and kaliyuretic effects of the drug. It is concluded that renal PG-system and kallikrein-kinin system are not involved in the formation of renal effects of dopamine. Renal tissue RAS directly included in the mechanism of action of dopamine in the kidney, acting as a modulator, preventing excessive loss of water and electrolytes with urine.

[Effect of the third generation beta-blockers on ion-regulating renal function in rats with heart failure model].

Beta-adrenoceptor blockers nebivolol and carvedilol do not affect diuresis and renal sodium excretion in intact rats, but significantly increase urinary excretion of sodium in animals with a model of heart failure caused by excessive physical exercise and injection of phenylephrine. Nebivolol, in contrast to carvedilol, causes additional increase the urinary potassium loss, which is retained in animals with experimental heart failure. It is concluded that both drugs increase renal sodium excretion in rats with heart failure model by preventing the excessive sodium delay in the body.

[Mechanism of action of catecholamines on sodium transport in sections of rat renal cortex]. / Mekhanizm deistviia katekholaminov na transport natrii v srezakh kory pochek krys.

Stimulation of renal beta-adrenoreceptors increased passive accumulation of sodium and water contents in cells of renal sections incubated in non-oxygenated medium without potassium and glucose but had no effect on the passive loss of potassiuna. During incibation of sodium loaded sections in oxygenated medium with potassium and glucose, stimulation of beta-adrenoreceptors increased excertion of sodium from the sections, and accumulation of potassium, which was followed by reducing of intracellular water. Activation of beta-adrenoreceptors during action of catecholamines seems to elicit an increased passive inflow of sodium into the cells of renal channels and to activate the ionic pump pumping away sodium in exchange for potassium.

[Role of the kallikrein-kinin system and prostaglandins in the action of dopamine on blood flow and sodium transport in the rat kidney]. / Rol' kallikrein-kininovoi sistemy i prostaglandinov v deistvie dofamina na krovotok i transport natriia v pochke krysy.

In anesthetized rats, dopamine (1 mg/kg) increased the blood flow in adrenal and external medullary layers of kidneys with accompanying obvious sodium-uretic response due to inhibition of sodium reabsorption, PO2 not changing, at that. Haloperidol (1 mg/kg) prevented the hemodynamic shift and its depressing effect on the sodium transport in the kidney channels. The inhibiting agent for kallikrein-kinin system contrical and inhibiting agent for prostaglandin synthetase indomethacin did not alter the kidney response to the neurotransmitter under study. The intrarenal hemodynamic shift and inhibition of sodium transport induced with dopamine seem to be due to stimulation of renal postsynaptic dopamine receptors and unrelated to activation of the renal kallikrein-kinin system or augmentation of prostaglandins synthesis.

[The interaction of the converting-enzyme inhibitor captopril with cardiac glycosides in the rat kidney]. / Vzaimodeistvie ingibitora konvertiruiushchego fermenta kaptoprila s serdechnymi glikozidami v pochke krysy.

Strophanthin (0.1 mg.kg, i.v.) and digoxin (0.1 mg/kg, i.v.) moderately increase blood supply of the renal cortical and medullary layers in unconscious rats and enhance renal excretion of sodium and water. Preadministration of the converting enzyme inhibitor captopril (10 mg/kg/day, per os, for 6 days) promoted vascular dilatation in the inner and outer areas of the medulla, which occurred under the action of these agents and substantially increased their natriuretic and diuretic effects. It is concluded that the renin-angiotension system is directly involved into the mechanism of action of cardiac glycosides in the kidneys, acting as a modulator that prevents their vasodilating and tubular effects.

[The interaction of the Ca2(+)-channel blocker verapamil with cardiac glycosides in the rat kidney]. / Vzaimodeistvie blokatora Ca2(+)-kanalov verapamila s serdechnymi glikozidami v pochke krysy.

Strophanthine (0.1 mg/kg, i. v.) and digoxin (0.1 mg/kg, i. v.) increase blood supply of the cortex and medullary layer of the kidneys of anesthetized rats and significantly raise excretion of water and sodium by the kidneys. Verapamil, a blocker of Ca(2+)-channels (0.25 mg/kg, i. v.) attenuates the increment of the blood flow in the internal zone of the cortex and external zone of the medullary layer but does not prevent the rise of diuresis and excretion of sodium with urine under the action of the above-indicated drugs. The conclusion is drawn that realization of the vasodilatory effect of cardiac glycosides in the kidneys is partially connected with a lowering of the content of Ca2+ in myofibrils whereas formation of their tubular effect does not depend on the changes in Ca2+ concentration in nephron cells.

[Effect of dopamine on the blood flow in various zones of the kidney cortex and medullary layer in rats]. / Vliianie dofamina na krotok v razlichnykh zonakh kory i mozgovogo sloia pochek krys.

Phentolamine and propranolol did not alter the kidney response to dopamine whereas haloperidol completely prevented the dopamine vascular and channel effects. The agents inhibiting cyclooxygenase and kallikrein-kinin system do not interfere with an increase in the blood flow or depressing action of the neurotransmitter upon sodium transport in the nephron. The hemodynamic shift occurring under the effect of dopamine in different areas of renal tissue seems to be due to a selective stimulation of vascular DA-receptors and unrelated to an increase in the production of prostaglandins and kinins in the kidneys.

[Effect of a blockade of the beta 1-adrenoreceptors on the hemodynamics, oxygen tension and sodium reabsorption in the rat kidney]. / Vliianie blokady beta 1-adrenoretseptorov na gemodinamiku, napriazhenie kisloroda i reabsorbtsiiu natriia v pochke krysy.

Blockade of kidneys' beta-1 adrenoreceptors with talinolol entailed in anesthetized rats a sodium- uretic response accompanied by inhibition of sodium reabsorption and an increase of the blood flow in cortical and external layers with no PO2 changes, at that. Haloperidol prevented the increase of blood flow in the external layer but did not affect the cortical hemodynamic shift or the depressing influence of talinolol on the channel transport of sodium. The inhibiting agent for the kallikrein-kinin system contrical and the inhibiting agent for prostaglandin synthesis indomethacin did not alter the kidney response to the drug under study. The hemodynamic shift as well as the inhibition of sodium reabsorption seem to be unrelated either to excitation of receptors sensitive to dopamine, or to activation of the kallikrein-kinin system or stimulation of prostaglandin synthesis.

[Effect of catecholamines on sodium resorption and oxygen tension in rat kidneys]. / Vliianie katekholaminov na reabsorbtsiiu natriia i napriazhenie kisloroda v pochke prys

Functional significance of alpha- and beta-adrenoreceptors for the mechanism of catecholamines effect on sodium reabsorption and oxygen tension in the rat kidney, was studied. Adrenaline inhibited sodium excretion decreasing its filtration in glomeruli and stimulating its reabsorption in tubules. The oxygen tension in these conditions did not change in the renal cortex while oxygenation of the external cortical layer was significantly increased. The blocking agent for alpha-adrenoreceptors phentolamin abolished the inhibiting effect of adrenaline on the glomerular filtration and somewhat decreased the degree of oxygen tension growth in the external cortical layer, leaving the tubular effect unaltered. The blocking agent for beta-adrenoreceptors inderal did not affect the inhibitory action of adrenaline on the glomerular filtration but completely prevented its activating effect on the tubular reabsorption of sodium and on oxygenation of the external cortical layer. A conclusion was drawn that catecholamines stimulation of sodium reabsorption in the rat kidney follows excitation of beta-adrenoreceptors. The increase in oxygen tension in the external cortical layer under effect of catecholamines is supposed to improve energetic supply of the sodium active transport in the ascending portion of the Henle loops.

[Stimulation by cyclic adenosine-3'5'-monophosphate by Na+, K+-activated ATPase from rabbit kidney]. / Stimuliatsiia (Na+ - K+)-aktiviruemoi ATF-azy pochek krolikov pod vliianiem tsiklicheskogo adenozin-3',5'-monofosfata

Cyclic 3',5-AMP in vitro increased the activity of Na+, K+-ATPase, isolated from cortex and medulla of rabbit kidney. Maximal stimulating effect was observed in kidney cortex at 10(-6) M concentration and in medulla at 10(-4) M concentration of 3',5'-AMP. Under these conditions the enzymatic activity was increased by 24.6 +/- 4.1% and 27.9 +/- 7.7%, respectively. These data suggest that Na+, K+-ATPase, activated by cyclic 3',5'-AMP, is directly involved in the mechanism of Na+ transport in cells of osmoregulating organs.

[The effect of antidiuretic hormone and catecholamines on transepithelial sodium transport]. / Vliianie antidiureticheskogo gormona i kateknolaminov na transépitelial'nyí transport natriia

Experiments were conducted on the isolated frog skin; it was shown that the activating action of pituitrin on the transepithelial transport of sodium decreased, and that of adrenaline increased with reduction of the concentration of this ion in the incubation medium. Strophanthine K, an inhibitor of (Na-+--K-+) -activated ATP-ase, prevented the activating effect of adrenaline on sodium transport, and in the medium with a low concentration of this ion--it only partially inhibited its actibating effect. A conclusion was drawn that the mechanisms of ADH and catecholamine activation of sodium transport by frog skin were not identical, although they had some common links. It is supposed that (Na-+--K-+)-activated ATP-ase was directly involved in the action mechanism of catecholamines on the system of active sodium transport in frog skin.

[Role of alpha- and beta-adrenoreceptors in catecholamine regulation of the natriuretic function of the kidneys in rats]. / Rol' alpha- i beta-adrenoretseptorov v reguliatsii katekholaminami natriiureticheskoi funktsii pochek krys.

In acute tests set up on rats subject to investigations was the significance of alpha- and beta-adrenoreceptors in the mechanism of the catecholamines influence on the natriuretic function of the rats' kidneys. Phentolamine did not obstruct the stimulating action of epinephrine on the tubular reabsorption of sodium, but perverted its inhibitory effect on the glomerular filtration. Inderal did not affect the glomerular action of epinephrine, but fully prevented its effect on reabsorption of sodium in the tubules of the kidney. When used in a dose failing to produce any significant changes in the systemic arterial pressure isopropylnorepinephrine increased glomerular filtration, but inhibited excretion of sodium, augmenting its tubular reabsorption. The resulting implication is that alpha-adrenoreceptors participate in the mechanism of the catecholamines regulation of the intrarenal hemodynamics, whereas beta-adrenoreceptors play the part of mediating their activating influence on the tubular transport of sodium.

[Effect of dopamine and its combination with furosemide on sodium transport in the rat kidney]. / Vliianie dofamina i ego kombinatsii s furosemidom na transport natriia v pochke krysy.

In experiments on rats phentolamine, propranolol, indomethacin were shown to exert no significant effect on the natriuretic action of dopamine, whereas haloperidol completely prevented it. In rats with chronic narrowing of the vena cava dopamine potentiated the diuretic and natriuretic effects of furosemide.

[Role of kidney prostaglandins, kinins and dopamine receptors in the natriuretic effect of ethacrynic acid]. / Rol' pochechnykh prostaglandinov, kininov i dofaminovykh retseptorov v natriiureticheskom éffekte étakrinovoi kisloty.

It was found in experiments on anesthetized rats that ethacrynic acid (3 mg/kg intravenously) exerted no effect on the blood flow in the internal zone of the cortical layer but significantly increased the blood supply to the median zone of this region of the kidneys. A pronounced natriuretic reaction produced by inhibition of this ion develops. An inhibitor of cyclooxygenase indomethacin (3 mg/kg orally, 5 days) completely eliminated an increase of the blood flow in the cortical median zone but failed to prevent an increase of diuresis and urinary excretion of sodium in response to the diuretic administration. An inhibitor of kallikrein contrykal (5000 U/kg subcutaneously) produced no effect on diuretic and natriuretic effects of the drug but prevented the hemodynamic shift in the renal cortex. A blocker of dopaminergic receptors haloperidol (3 mg/kg subcutaneously) caused no changes in the rat kidney response to ethacrynic acid. Prostaglandins and kinins formed in the kidneys under the influence of the diuretic are thought to be involved in the mechanism of dilatation of vessels of the cortical layer median zone but play no significant role in the formation of its natriuretic effect.

[Interaction of catecholamines and the renin-angiotensin system in regulating sodium reabsorption in the rat kidney]. / Vzaimodeistvie katekholaminov i sistemy renin-angiotenzin v reguliatsii reabsorbtsii natriia v pochke krysy.

It has been established that the catecholamine-induced increase in renin secretion by juxtaglomerular apparatus cells and sodium reabsorption stimulation in the rat kidney are consequent on the excitation of renal beta-adrenoreceptors. Strophanthin K interferes with the renin-secreting action of adrenaline and perverts its activating effect on sodium transport by renal tubules. When given in a dose inhibiting angiotensin II formation and renin-secreting effect of catecholamines, heparin also diminishes their activating effect on tubular sodium transport. It is suggested that the renin-angiotensin system may be directly involved into the mechanism of catecholamine-stimulated sodium reabsorption by the rat kidney.

[Effect of diuretics on catecholamine stimulation of sodium reabsorption in the rat kidney]. / Vliianie nekotorykh diuretikov na stimuliatsiiu katekholaminami reabsorbtsii natriia v pochke krysy.

To analyze the mechanism of the catecholamines activation of the tubular sodium transport the response of the rat's kidney to epinephrine under the action of some diuretics was investigated. Triamteren, an inhibitor of the lumenal membrane permeability to sodium, considerably weakened the stimulating effect of epinephrine on the sodium reabsorption in the renal tubules. Etacrynic acid which blocks one of the components in the system of active sodium transport in the tubular epithelium cells did not influence the activating effect of epinephrine. Strophanthin K, an inhibitor of the (Na+-K+)-activated ATP-ase completely prevented any accretion of the tubular sodium reabsorption under the effect of epinephrine. It is inferred that catecholamines can act directly on some components of the system reabsorbin sodium in renal tubules of the rat.