Reinvestigation of denervation diuresis and natriuresis in conscious dogs.

The function of innervated and denervated kidney was compared in clearance studies with conscious dogs. The animals were prepared for experiments by unilateral renal denervation and surgical division of the bladder to form two hemibladders enabling separate urine collection from two kidneys. The mean urine flow was 6% higher for the denervated kidney (not significant) while mean differences for osmolar clearance (+ 13%), sodium excretion (+21%) and GFT (+5%) were all significant (P less than 0.05). When corrected to 100 ml GFR, sodium excretion was not significantly higher for the denervated kidney. In most experiments higher sodium excretion on the denefvated side was associated with higher GFR. Thus, contrary to some earlier views, a slight increase in the excretory function which follows denervation of the kidney is demonstrable also in conscious undisturbed animals. The data suggest that increased haemodynamics of the denervated kidney are responsible for higher excretion, but do not exclude a contribution of inhibited tubular reabsorption.     

Sleep deprivation induces the unfolded protein response in mouse cerebral cortex

Little is known about the molecular mechanisms underlying sleep. We show the induction of key regulatory proteins in a cellular protective pathway, the unfolded protein response (UPR), following 6 h of induced wakefulness. Using C57/B6 male mice maintained on a 12:12 light/dark cycle, we examined, in cerebral cortex, the effect of different durations of prolonged wakefulness (0, 3, 6, 9 and 12 h) from the beginning of the lights-on inactivity period, on the protein expression of BiP/GRP78, a chaperone and classical UPR marker. BiP/GRP78 expression is increased with increasing durations of sleep deprivation (6, 9 and 12 h). There is no change in BiP/GRP78 levels in handling control experiments carried out during the lights-off period. PERK, the transmembrane kinase responsible for attenuating protein synthesis, which is negatively regulated by binding to BiP/GRP78, is activated by dissociation from BiP/GRP78 and by autophosphorylation. There is phosphorylation of the elongation initiation factor 2alpha and alteration in ribosomal function. These changes are first observed after 6 h of induced wakefulness. Thus, prolonging wakefulness beyond a certain duration induces the UPR indicating a physiological limit to wakefulness.     

Time course of denervation diuresis and natriuresis in the anaesthetized rat

The effect of unilateral renal sympathectomy on renal excretion of water and sodium was studied in three groups of Inactin-anaesthetized rats: 1-3, 4-19, and 20-35 weeks after denervation. Increased sodium excretion from the denervated kidney in the absence of changes in GFR was observed up to 35 weeks following renal denervation. Thus, in a functional sense, renal reinnervation may have only been partial during the time interval studied.     

The role of nitric oxide in saline-induced natriuresis and diuresis in rats.

This study was designed to determine to what extent nitric oxide (NO) mediates the natriuretic and diuretic responses to acute isotonic saline (0.9 gram % NaCl) volume expansion (SVE, 0.5 ml min-1 kg-1). Studies were performed on 49 pentobarbital anesthetized (65 mg/kg) female Sprague-Dawley rats with or without a NO synthase inhibitor, Nomega-nitro-L-arginine (LNA). Group 1 received saline at 27 microliter/min for 1 hr (baseline) and then SVE for 1 hr; Groups 2-4 received LNA at 10, 150, and 200 microgram kg-1 min-1, respectively, for 1 hr followed by LNA + SVE. To determine to what extent inhibition of NOS would reverse an ongoing SVE-induced natriuresis and diuresis, Group 5 was saline-volume-expanded for hours 1 and 2 whereas Group 6 was administered SVE during the first hour and then SVE + 150 microgram kg -1 min-1 LNA during the second hour. SVE caused a significant (P < 0.05) increase in the glomerular filtration rate (GFR) of Group 1 and the LNA-treated rats (Groups 2-4). This SVE-induced increase in the GFR occurred despite the fact that baseline GFR was significantly lower in the two groups of rats that were infused with the highest doses of LNA (Groups 3-4). SVE was also associated with similar increases in urine flow rate, sodium and potassium excretion, and total osmolar excretion in Groups 1-4. On the other hand, mean arterial pressure (MAP) was significantly higher in Group 2 during SVE + LNA and during the baseline as well as during the SVE periods in Groups 3-4; MAP was also significantly elevated in Group 6 during SVE + LNA. Thus, despite the fact that MAP was higher in LNA-treated rats, sodium and urine flow rates were the same as in Group 1 (i.e., there was no evidence of a pressure natriuresis or diuresis in these animals). Along these lines, there was a small but significant positive linear correlation coefficient (r = 0.41, P = 0.05) between sodium excretion values and corresponding MAP values in SVE control rats but not in Groups 3-4 during SVE (r = 0.28, P = 0.26). The current data demonstrate that 1) NO does not mediate SVE-induced hyperfiltration in the rat, 2) NO also does not mediate SVE-induced natriuresis or diuresis, and 3), consistent with other reports, NO appears to mediate pressure natriuresis and diuresis.     

Regulation of arterial pressure: role of pressure natriuresis and diuresis

The importance of the renal pressure natriuresis and diuresis mechanisms in long-term control of body fluid volumes and arterial pressure has been controversial and difficult to quantitate experimentally. Recent studies, however, have demonstrated that in several forms of chronic hypertension caused by aldosterone, angiotensin II (AngII), vasopressin, or norepinephrine and adrenocorticotropin, increased renal arterial pressure is essential for maintaining normal excretion of sodium and water in the face of reduced renal excretory capability. When renal arterial pressure was servo-controlled in these models of hypertension, sodium and water retention continued unabated, causing ascites, pulmonary edema, or even complete circulatory collapse within a few days. Apparently, other mechanisms for volume homeostasis, such as the various natriuretic and diuretic factors that have been postulated, are not sufficiently powerful to maintain fluid balance in the absence of increased renal arterial pressure when renal excretory function is reduced in these forms of hypertension. The intrarenal mechanisms responsible for pressure natriuresis and diuresis are not entirely clear, but they seem to involve small increases in glomerular filtration rate and filtered load as well as reductions in fractional reabsorption in proximal and distal tubules. During chronic disturbances of arterial pressure additional factors, especially changes in AngII and aldosterone formation, act to amplify the effectiveness of the basic renal pressure natriuresis and diuresis mechanisms in regulating arterial pressure and body fluid volumes.     

兔室旁核对血量扩张引起促钠排泄与利尿的作用

在室旁核(PVN)假损毁兔与PVN损毁兔血量扩张(VE)引起尿流量增加,峰值分别为0.59±0.09与0.31±0.03 ml/min (P<0.01),排钠量增加峰值分别为66.76±6.74与36.05±3.44μmol/min (P<0.01),而在PVN假损毁兔与PVN完好兔对VE的反应无显著差别(P>0.05),表明PVN损伤可明显减弱 VE 引起的促钠排泄与利尿效应.颈迷走神经切断并不能改变 PVN损伤的上述作用.双侧肾神经切断兔损毁 PVN对VE引起促钠排泄效应无显著影响,但显著减弱其利尿效应 (P<0.02).PVN损毁对VE时肾小球滤过率(GFR)与肾血浆流量(RPF)无显著影响.结果表明PVN参与VE通过迷走传入神经引起促钠排泄与利尿反应的调节,而肾交感传出神经参与其中促钠排泄的作用.     

兔室旁核对血量扩张引起促纳排泄与利尿的作用

在室旁核 (PVN)假损毁兔与PVN损毁兔血量扩张 (VE)引起尿流量增加 ,峰值分别为 0 5 9± 0 0 9与0 3 1± 0 0 3ml/min (P <0 0 1) ,排钠量增加峰值分别为 66 76± 6 74与 3 6 0 5± 3 4 4μmol/min (P <0 0 1) ,而在PVN假损毁兔与PVN完好兔对VE的反应无显著差别 (P >0 0 5 ) ,表明PVN损伤可明显减弱VE引起的促钠排泄与利尿效应。颈迷走神经切断并不能改变PVN损伤的上述作用。双侧肾神经切断兔损毁PVN对VE引起促钠排泄效应无显著影响 ,但显著减弱其利尿效应 (P <0 0 2 )。PVN损毁对VE时肾小球滤过率 (GFR)与肾血浆流量 (RPF)无显著影响。结果表明PVN参与VE通过迷走传入神经引起促钠排泄与利尿反应的调节 ,而肾交感传出神经参与其中促钠排泄的作用     

Caffeine-induced natriuresis and diuresis via blockade of hepatic adenosine-mediated sensory nerves and a hepatorenal reflex

The hepatorenal reflex, activated by intrahepatic adenosine, is involved in the regulation of urine production in healthy rats and renal pathogenesis secondary to liver injury. Hepatic adenosine A1 receptors regulate the hepatorenal reflex. The aim of the present study was to evaluate whether caffeine mediates renal natriuresis and diuresis in healthy and diseased liver through this mechanism. Rats were anesthetized and instrumented to monitor systemic, hepatic, and renal circulation and urine production. Intrahepatic (intraportal but not intravenous) caffeine (5 mg·kg-1) increased urine flow (~82%) in healthy rats. This effect was abolished by liver denervation. Intraportal infusion of adenosine decreased urine production, and this response was abolished by intraportal but not intravenous caffeine. Liver injury was induced by intraperitoneal injection of thioacetamide (500 mg·kg-1), and functional assessment was performed 24 h later. Liver injury was associated with lower (~30%) glomerular filtration rate, lower (~18%) renal arterial blood flow, and lower urine production. Intraportal but not intravenous caffeine improved basal urine production and renal ability to increase urine production in response to saline overload. The liver-dependent diuretic effect of caffeine is consistent with the hypothesis for the adenosine-mediated mechanism of hepatorenal syndrome.     

大鼠脑胆碱能系统对血量扩张引起利尿与尿钠排泄...

The role of brain cholinergic system on diuresis and natriuresis induced by volume expansion was studied in conscious rats. In a series of experiments, the diuretic, natriuretic and kaliuretic responses induced by volume expansion were compared in three groups of conscious rats pretreated respectively with intracerebroventricular (icv) injection of artificial cerebrospinal fluid (ACSF), atropine and hexamethonium. The natriuretic, kaliuretic and diuretic responses induced by volume expansion were much less in the animals with icv injection of atropine than in the control group with injection of ACSF (P less than 0.01). While the group pretreated with icv injection of hexamethonium showed no significant decrease in these responses of volume expansion than that of the control (P greater than 0.05). Volume expansion produced no change in insulin and PAH clearance in both the atropine and the ACSF group. Thus the atropine suppressed diuresis, natriuresis and kaliuresis are independent of changes in GFR and RPF. It is inferred from the results of the present investigation that volume expansion induced diuresis and natriuresis appear to be due to inhibition of water and sodium reabsorption in the renal tubules and regulated by certain brain cholinergic system.     

Bilateral acute heart atrial auriectomy reduced diuresis and natriuresis following hypertonic sodium load in anaesthetized dogs

Anaesthetized dogs were deprived of a portion of the atrial natriuretic factor producing tissue by bilateral acute heart atrial auriectomy. Their ability to respond by diuresis and natriuresis either to the expansion of extracellular fluid volume with isotonic saline (3% b.w.) or to hyperosmolality induced by hypertonic saline loading (0.13% b.w. of 20% NaCl solution) was subsequently reduced by about 50%. It is thus suggested that atrial natriuretic system may also play a role in osmoregulation by taking part in the promotion of renal sodium excretion.     

Propranolol induces acute natriuresis by beta blockade and dopaminergic stimulation.

dl-Propranolol (0.8-1.6 mg/kg - h for 1 h) produced a transient two- to three-fold increase in sodium excretion in nondiuretic rats infused with Pitressin and aldosterone and in water diuretic rats. Sodium excretion increased more in rats depleted of renin by chronic Doca and salt administration than in rats maintained on a low salt diet. An angiotensin inhibitor (1,sarcosine-8,valine angiotensin II) decreased sodium excretion. Therefore the natriuresis was not mediated by antidiuretic hormone, aldosterone, or renin-angiotensin. d-Propranolol did not produce a natriuresis. Prior treatment with phenoxybenzamine did not prevent the natriuretic response but chlorisondamine pretreatment did. The natriuresis is produced by beta blockade and requires post ganglionic nerve function but is independent of alpha receptors. dl-Propranolol decreased heart rate and cardiac output but systemic pressure did not fall and renal blood flow increased. This suggests a dopamine-mediated renal vasodilation and natriuresis. Haloperidol and pimozide, both dopamine blocking agents with minimal beta blocking effects, prevented the natriuretic response. We conclude that propranolol may increase sodium excretion directly by blocking beta receptors in the distal nephron and indirectly by dopamine-mediated renal vasodilation.     

Effect of the time of theophylline administration on the intensity of diuresis and natriuresis in the rat]

The present study originates in two experimental data: circadian variations evidence of water, electrolytes and solutes urinary excretion and theophylline diuretic and salidiuretic effects knowledge; we purpose to evidence theophylline-induced water and sodium renal excretion in rats as modified by the time of drug administration. Theophylline single dose is injected in 100 animals (20 lots of 5 rats) at 8 h, 14 h, 20 h or 2 h and urines are collected during a consecutive to injection hours long period: 8 h-14 h (I), 14 h-20 h (II), 20 h-2 h (III) or 2 h-8 h (IV). Diuresis increases in + 40,4 p. cent (I), in + 123,7 p. cent (II), in + 123,3 p. cent (III) in + 65,4 p. cent (IV). So, natriuresis increases in 39,6 p. cent (I), in 223,2 p. cent (II), in 114,3 p cent (III) and in 109,6 p. cent (IV). These results evidence that theophylline diuretic and natriuretic effects change strongly with injection time, being largest if it is injected at 14 h and slightest if injected at 8 h. Such observations prompt to study if the other pharmacological properties of theophylline, especially at pulmonary level, response also with a time-dependant intensity.