Effect of destruction of the posterior pituitary on the diuresis from left atrial receptors.

1. In anaesthetized dogs, stimulation of atrial receptors after destruction of the pituitary gland results in a diuresis. This response was not abolished by the administration of bretylium tosylate and was also observed in a surgically denervated kidney. 2. The diuresis is qualitatively similar to that observed in anaesthetized dogs with intact pituitary glands. 3. It is concluded that the diuresis which results from stimulation of the left atrial receptors is mediated by a blood-borne agent which is not the antidiuretic hormone.     

On the mechanism of compensatory diuresis following unilateral nephrectomy in dogs

Summary The antidiuretic activity of blood plasma in dogs was studied (by means of tests on rats) prior to, and 1–2 hours after unilateral nephrectomy. The antidiuretic activity of dog plasma declines directly after the operation. The blood plasma obtained from dogs prior to the operation inhibits the excretion of water load in the rats.Changes in the antidiuretic activity of blood plasma are regarded as being the result of the reflex effects from the vascular and tissue osmoreceptors in connection with increased amounts of extracellular water, directly after nephrectomy. It is therefore concluded that reduction of the plasma antidiuretic activity is an important factor in the mechanism of diuresis compensation directly after unilateral nephrectomy.(Presented by Active Member Akad. Med. Nauk SSSR A. V. Lebedinskii) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 52, No. 12, pp. 28–30, December, 1961     

Renal effects of left atrial distension in dogs with chronic congestive heart failure.

The renal response to left atrial balloon inflation in normal dogs was compared with that in dogs with chronic congestive heart failure (CHF). CHF was induced by the production of an aortocaval fistula below the level of the renal arteries. CHF dogs showed elevated left ventricular end-diastolic pressure, enlarged hearts, a depression of myocardial contractility, pulmonary edema, ascites, and peripheral edema. They also showed significant decreases in urine flow, creatinine clearance, para-aminohippurate clearance, sodium and potassium excretion, fractional sodium excretion, osmolar clearance, arterial blood pressure, and heart rate. Balloon distension of the left atrium evoked a significant increase in urine flow and free-water clearance in the normal group. The reflex nature of this response was indicated by its blockade after bilateral cervical vagotomy. In contrast, the CHF group did not exhibit significant changes in urine flow or free-water clearance during balloon inflation. Plasma antidiuretic hormone (ADH) was significantly elevated in the CHF group; however, balloon distension reduced plasma ADH in both groups of dogs. Plasma renin activity was significantly elevated in the CHF dogs and was not changed by balloon distension in either group of dogs. It is concluded that animals with high-output CHF do not exhibit the atrial-diuretic reflex in spite of their ability to reduce ADH levels by atrial distension.     

The role of antidiuretic hormone in cold-induced diuresis in the anaesthetized rat

The aim of this study was to investigate whether the increased diuresis in consequence of hypothermia is due to a depression of the hypothalamic release of antidiuretic hormone (ADH). The plasma concentration of antidiuretic hormone and the effect of intravenous (i.v.) administration of 65 ng kg^?1 desmopressin (selective V₂-receptor agonist) were determined in the anaesthetized rat. In spite of a 50% (P < 0.001) decrease in glomerular filtration rate, urine flow increased sixfold (P < 0.01) and urine sodium excretion increased sevenfold (P < 0.05), whereas urine osmolality decreased (P < 0.001). At the same time plasma antidiuretic hormone decreased from 7.5 ± 1.1 to 3.8 ± 0.4 pg mL^?1 (P = 0.01). After injection of desmopressin urine flow was completely restored, whereas urine osmolality and sodium excretion were only partially normalized. Since tubular conservation of water and fractional water reabsorption decreased during hypothermia, the diuresis must have resulted from an augmented loss of water. This is further supported by the fact that osmolal excretion was not influenced either by hypothermia or by desmopressin. It is concluded that the diuresis in consequence to hypothermia is due both to a decrease in the release of ADH and to a reduction of renal medullary hypertonicity.     

Gradation of the reflex response from atrial receptors.

1. In anaesthetized dogs, distension of balloons so as to stimulate atrial receptors resulted in a reflex increase in heart rate. 2. Successive distensions of one, two and three balloons positioned in the left upper and middle pulmonary vein-atrial junctions and in the left atrial appendage resulted in a progressive increase in the magnitude of this response. 3. It is concluded that the magnitude of the increase in heart rate is related to the extent of receptor area stimulated.     

An attempt to quantitate the contribution of antidiuretic hormone to the diuresis of left atrial distension in conscious dogs

In order to quantitate the contribution of the antidiuretic hormone (ADH) to the diuresis of left atrial distension 52 experiments have been performed in 12 conscious, chronically instrumented beagle dogs. Left atrial pressure was increased by a reversible mitral stenosis by about 10 cm H₂O (1.0 kPa) for 60 min. Plasma ADH concentration (range between 1.3 and 6.0 pg·ml^?1) (radioimmunoassay) decreased in every experiment, the average decrease being about 50%. An i. v. infusion of vasopressin (0.05 mU ·min^?1·kg^?1) abolished the diuretic effect of left atrial distension or decreased the urine volume below control values; natriuresis was not affected. The magnitude of the vasopressin effect was dependent on the concurrent sodium excretion: when sodium excretion was low during left atrial distension, vasopressin was more effective in reducing the urine volume than when sodium excretion was high. It is concluded that the diuresis of left atrial distension is mediated (a) by a suppression of ADH and (b) by factors controlling sodium excretion, the contribution of these two mechanisms being dependent on the concurrent sodium excretion.     

Effect of stimulating right atrial receptors on urine flow in the dog

1. Complex unencapsulated nerve endings (right atrial receptors) have previously been found in the endocardium of the right atrial appendage and the junction between the superior vena cava and the right atrium.2. Distension of balloons located in the right atrial appendage and at the junction between the superior vena cava and the right atrium resulted in an increase in urine flow. This diuresis was accompanied by a small increase in the excretion of sodium.3. Cooling the right cervical vagus caused a reduction in the response to distension of the right atrial appendage.4. It is concluded that stimulation of right atrial receptors by the distension of balloons located in the right atrial appendage and at the junction between the right atrium and the superior vena cava results in a reflex increase in urine flow.     

The relationship between left atrial pressure and atrial receptor discharge in dogs and cats with different body weights

The diuretic response to distension of a large balloon in the left atrium and the increase in discharge of atrial receptors for a given increment in left atrial pressure have been found to be greater in dogs with a high blood volume than in dogs with a low blood volume. To determine whether atrial size may influence atrial receptor discharge, a group of cats and two groups of dogs with different body weights were examined under anaesthesia with alpha-chloralose. The relationship between atrial receptor discharge and left atrial pressure was determined in twenty-six fibres from seven cats, thirty-seven fibres from eight small dogs weighing less than 15 kg and twenty-five fibres from five large dogs weighing more than 25 kg. The slope of the relationship between the increase in atrial receptor activity and increments in left atrial pressure was shown to be significantly greater in the large dogs than in the small dogs, and the slopes in dogs were greater than in cats. The size of the atria was greater in larger dogs than small, and both those groups had atria larger than those of the cats. These findings indicate that the response of an increase in atrial receptor discharge to the same increment in left atrial pressure was greater in large animals than small and that this difference is possibly due to the different atrial size.     

Depression of the reflex tachycardia from the left atrial receptors by acidaemia

1. The effects are described of an acidaemia, produced either by the inhalation of carbon dioxide or by an intravenous infusion of hydrochloric acid, on the reflex increase in heart rate which results from stimulation of the left atrial receptors in the anaesthetized dog.2. The results show that during acidaemia the reflex increase in heart rate from stimulation of the left atrial receptors is reduced. The extent of the reduction is related to the degree of the acidaemia.3. It is suggested that it is necessary to monitor and correct changes in the pH of arterial blood in experiments which involve reflex changes in heart rate, especially if the efferent pathway involves the sympathetic nerves.4. It is also suggested that the occurrence of such an acidaemia in anaesthetized surgically traumatized animals may be a factor contributing to the variability in results from investigations involving reflex changes in heart rate in response to stimulation of the left side of the heart.     

The role of the cardiac nerves in the regulation of sodium excretion in conscious dogs

Conscious, chronically instrumented dogs, maintained on a high sodium intake, were used to investigate whether surgical cardiac denervation impairs the natriuresis associated with left atrial pressure increase produced in three ways: during an increase in left atrial pressure by means of a reversible mitral stenosis (protocol 1); after an i.v. saline load (1.0 ml 0.9%·saline min^–1·kg^–1 over 60 min) (protocol 2); after an oral saline load (14.5 mmol Na·kg^–1 given with the food as an isotonic solution) (protocol 3).During a reversible mitral stenosis, in intact dogs, urine volume and sodium excretion increased markedly (from 34–145 l·min^–1·kg^–1 and from 3–12 mol·min^–1·kg^–1); mean arterial pressure increased by an average of 2 kPa (15 mm Hg) and heart rate by 55 b/min; plasma renin activity fell from 0.37–0.21 ng Al·ml^–1·h^–1. Cardiac denervation eliminated these effects of left atrial distension except for a small increase in heart rate (12 b/min). This indicates that the natriuresis and diuresis during left atrial distension resulted from stimulation of receptors located in the left atrium.In contrast, during protocol 2 and 3, the same amounts of sodium and water were excreted in the cardiac denervated dogs as compared to the intact dogs. A comparable decrease in plasma renin activity also was observed. — Apparently the presence of the cardiac nerves is not a prerequisite for maintenance of sodium and water homeostasis.     

Role of atrial receptors in the control of ACTH.

Sinusoidal volume changes (+/- 1 ml) were applied at 1 Hz to the right or left atrium of 25 anesthetized cats. Changes in firing rates of single vagal fibers and in plasma ACTH and cortisol were observed in response to start and stop of atrial pulsation. Decreased activity of right atrial and/or septal B-receptors was associated with increased ACTH. Changes in left atrial B-receptor activity were associated with a change in ACTH only if right atrial/septal receptors or baroreceptors also changed their activity in the same direction. The activity of atrial A-receptors did not change in response to atrial pulsation. A quantitative analysis suggested strongly that right atrial and/or septal B-receptors dominate in the response of ACTH to hemodynamic stimuli. Arterial receptors appear less effective, and left atrial B-receptors appear least effective in the hemodynamic control of ACTH.     

The relation between carotid solute concentration and renal water excretion in conscious dogs

Verney's hypothesis of cerebral osmoreceptors controlling the renal excretion of water via vasopressin was reinvestigated in conscious trained dogs provided with bilateral skin loops containing the common carotid arteries. In multiple experiments in two dogs, bilateral intracarotid injections (0.25 ml.(kg b. wt.)^-1 per artery in 10 s) of a hyperosmotic solution of sodium chloride (0.257 mol/l) during transient water diuresis failed to produce an antidiuretic response, although it is estimated that the injections elevated the osmolality of the carotid blood by 12–15%. In another 5 dogs, bilateral intracarotid infusions of hyperosmotic saline (45 μmol. (kg b. wt. min)^-1 per artery for 10 min) during sustained water diuresis resulted in a 3% increase in jugular venous osmolality and an antidiuretic response without detectable changes in heart rate or mean arterial pressure. Equal intravenous hyperosmotic or intracarotid isosmotic infusions were not associated with antidiuretic responses. Analysis of the concomitant concentrations of vasopressin in plasma fell short of supporting the hypothesis that the antidiuretic response to intracarotid hyperosmotic infusions was exclusively or mainly due to liberation of vasopressin. although the renal response could be mimicked by exogenous vasopressin. It is concluded that the present results—although discordant with several of Verney's results and assumptions—nevertheless support the concept of a cerebral solute receptor influencing the rate of renal water excretion.     

The activity of the hypothalamo-hypophysial Antidiuretic system in conscious dogs

Summary The influence of isoosmotic changes of blood volume on plasma vasopressin level, osmotic reactivity f the antidiuretic system, central venous pressure, arterial blood pressure and heart rate was examined in ten conscious dogs after left—sided cervical vagosympathectomy. A moderate decrease of the blood volume by 15% produced only a slight and transient rise of the plasma vasopressin level and heart rate. Mean arterial blood pressure decreased under the same conditions. A moderate increase of the blood volume by 15% influenced neither the spontaneous activity nor the osmotic reactivity of the antidiuretic system in the same dogs. An increase of central venous and mean arterial pressure was observed under these conditions.The result suggest that the most sensitive receptors susceptible to moderate blood volume changes and influencing the activity of the antidiuretic system are located in the region of distribution of the left vagosympathetic afferents.     

The role of left atrial receptors in the diuretic response to left atrial distension

1. The diuretic response to distension of the whole left atrium caused by obstruction of the mitral orifice has been compared with the effects of distension (by means of small balloons) of the left pulmonary vein/left atrial junctions.

2. Distension of the pulmonary vein/atrial junctions caused an increase in heart rate and a diuresis similar to but smaller than that caused by mitral obstruction.

3. Section of both ansae subclaviae prevented the increase in heart rate produced by distension of the pulmonary vein/left atrial junctions but had little effect on the diuretic response either to pulmonary vein distension or to mitral obstruction.

4. A diuretic response to mitral obstruction could be demonstrated after all nerves from the lungs had been cut but not after the vagus nerves had been cut at levels likely to interrupt the majority of afferent fibres from left atrial receptors.

5. The results support the view that stimulation of left atrial receptors is a major factor in the production of a diuretic response to mitral obstruction.

     

Effects of carotid occlusion and left atrial stretch on supraoptic neurosecretory cells.

Acute experiments were performed on pentobarbital-anesthetized cats to determine whether atrial and carotid baroreceptors affected the same neurosecretory neurons in the supraoptic nucleus (SON) of the hypothalamus. The osmosensitivity of these neurons was also determined. Eighty-two SON neurons were antidromically identified and 63 of these increased their firing rates during complete occlusion of the right carotid artery. Further testing of these 63 neurons demonstrated that 56 were inhibited by directly stretching the left atrium and 61 were excited by intracarotid injection of hypertonic saline. Left atrial stretch greatly reduced the neuronal response to carotid occlusion. These results show that the activity of the majority of the antidromically identified SON neurons is altered by left atrial and carotid artery receptors as well as changes in plasma osmolality. Results are consistent with the known influence of these receptors on plasma vasopressin.     

Left atrial receptors in arterial baroreflex control of heart rate

We have studied the influence of left atrial receptor stimulation on arterial baroreflex control of heart rate with a view to determine the role of cardiac efferent sympathetic and parasympathetic pathways in any interaction observed. Experiments were performed on anaesthetized, artificially ventilated, and thoracotomised cats and dogs. The sensitivity of baroreflex heart rate response was found to be higher in dogs as compared to cats. Both the sympathetic and parasympathetic effects contributed to the reflex chronotropic effects observed during changes in mean arterial blood pressure. The reflex tachycardia response during left atrial receptor stimulation was more pronounced in dogs than in cats. Stimulation of left atrial receptors caused slight inhibition of the baroreflex tachycardia response and potentiation of the bradycardia response.     

The relationship between plasma vasopressin concentration and urinary excretion during left atrial distension in anaesthetized dogs

The relationship between the changes in plasma vasopressin (AVP) concentration and urinary concentration during left atrial distension has been examined in 12 anaesthetized dogs. Left atrial pressure was increased by 1.2 kPa for 30 min. Plasma AVP concentration (radioimmunoassay) was decreased 5 min after the start of atrial distension and was increased again 5 min after the end of distension. The average decrease was about 50% from a mean of 6.4±2.4 pg · ml^–1 (SE). Urine osmolality decreased more slowly reaching its lowest value in the first 10 min after removal of atrial distension. In contrast sodium excretion increased immediately upon atrial distension. Because of the difference in the time course of the changes in plasma AVP and urine osmolality, plasma AVP was compared with the urine osmolality in samples collected 15 min after the plasma samples. At any plasma AVP concentration there was a wide variation in urine osmolality between dogs, but in any one dog there was clear relationship between plasma AVP and urine osmolality. The results support the view that the diuretic response to left atrial distension is due, at least in part to decreases in plasma AVP concentration. They also show that a stimulus arising from increased left atrial pressure influences the relationship between plasma osmolality and plasma AVP concentration.     

MicroRNA-29a、-133a在持续性房颤模型犬心房肌中的表达变化

 目的：构建持续性心房颤动(AF)犬模型,观察其心房肌组织microRNA-29a、-133a表达及其与AF和心肌纤维化的关系。方法：采用慢性快速心房起搏诱发持续性心房颤动犬模型,并设置假手术组。应用心脏超声测量心脏结构大小,通过Masson三色法染色计算胶原容积分数来评估纤维化程度,采用实时荧光定量-聚合酶链反应（real-time PCR）检测左心房(LA)肌microRNA-29a、-133a的水平。结果：持续性心房颤动模型犬造模后与造模前相比,心房内径和射血分数无统计学意义（P＞0.05）;与假手术组相比,持续性心房颤动模型组心房肌纤维化程度明显增高,胶原容积分数（CVF）明显增加(P＜0.01),且microRNA-29a、-133a表达水平明显下降(P＜0.01,P＜0.05)。结论：心房结构重构及心房肌纤维化是心房颤动发生及维持的重要基础,microRNA-29a、-133a表达水平下调可能是持续性心房颤动模型犬左心房结构重构的分子机制之一。     

Influence of histamine and antidiuretic hormone on diuresis and renal excretion of the enzyme hyaluronidase

Summary Experiments on dogs with ureters exposed by Pavlov's method were used to study the influence of a single intravenous injection of histamine and antidiuretic hormone (pituitrin) on the water excreting function of the kidney and excretion of hyaluronidase enzyme with urine. It was established that injection of histamine as well as of antidiuretic hormone caused a reduction in diuresis with a simultaneous appearance of hyaluronidase enzyme in the urine; at the same time, as the enzyme concentration in the urine became greater the more considerable was the reduction of diuresis.The results of the investigations give ground to suppose that the antidiuretic effect of histamine on the kidney is partly due to the presence of hyaluronidase enzyme.(Presented by Member of the Academy of Medical Sciences of the USSR V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 61, No. 5, pp. 15–18, May, 1966