Effect of catecholamines on tubular function in the isolated perfused rat kidney

1977 ◽  
Vol 233 (1) ◽  
pp. F39-F45 ◽  
Author(s):  
A. Besarab ◽  
P. Silva ◽  
L. Landsberg ◽  
F. H. Epstein

Addition of norepinephrine or epinephrine to the isolated rat kidney perfused at constant pressure resulted in an increase in sodium reabsorption and the excretion of a dilute urine with an increase in free water clearance. Vasopressin reversed the fall in urinary osmolarity but not the diminution in sodium excretion. The urinary changes produced by catecholamines were blocked by propranolol but not by phenoxybenzamine, suggesting that they were mediated, at least in part, by beta receptors. Similar though less pronounced changes in sodium excretion and urinary osmolarity were produced by isoproterenol and phenylephrine, while the combination of these drugs induced marked dilution of the urine. The results suggest that circulating catecholamines or adrenergic nerves innervating the kidney directly influence renal tubular function and might, therefore, participate in the regulation of sodium and water excretion by the kidneys.

1977 ◽  
Vol 232 (1) ◽  
pp. F16-F19
Author(s):  
G. Nomura ◽  
T. Takabatake ◽  
S. Arai ◽  
D. Uno ◽  
M. Shimao ◽  
...  

The effects of acute denervation of the kidney on renal tubular sodium and water excretion were studied in anesthetized, hypophysectomized, and cortisone-treated mongrel dogs during stable water diuresis produced by the infusion of 2.5% dextrose. In all experiments, denervation natriuresis, and diuresis were observed without significant change in glomerular filtration rate (GRF) and renal plasma flow (RPF). Fractional sodium delivery to the distal nephron (CNa + CH2O/100 ml GFR) and fractional free water clearance (CH23/100 ml GFR) was significantly greater in the denervated kidney compared with the innervated kidney (9.6+/-1.2 vs. 6.7+/-0.9% and 8.8+/-1.2 vs. 6.5+/-0.8%, respectively). Distal tubular sodium reabsorption (CH2O/(CNa + CH2O)) was not significantly different. We conclude that renal denervation primarily affects the proximal tubule as manifested by a decrease in the reabsorption of sodium and water. A small effect of denervation on the distal nephron is not completely ruled out.


1981 ◽  
Vol 240 (6) ◽  
pp. F522-F529
Author(s):  
C. Westenfelder ◽  
R. K. Hamburger ◽  
M. E. Garcia

Orthovanadate (VO4) has been shown to cause a marked natriuresis in rats. This has been ascribed to its inhibitory action on renal Na-K-ATPase activity. Because virtually all nephron segments possess Na-K-ATPase activity the administration of VO4 should alter renal tubular transport along the entire nephron. To examine this possibility, adult rats were anesthetized and infused with VO4 (10 mumol.kg body wt-1.h-1 i.v.). This dose had no effect on glomerular filtration rate, effective renal plasma flow, and blood pressure, whereas urine flow and sodium and water excretion rose markedly. Potassium excretion remained unaltered. VO4 depressed only maximal bicarbonate and glucose reabsorption without causing a glucose or bicarbonate "leak" at normal levels of blood glucose or bicarbonate. In acutely thyroparathyroidectomized rats VO4 produced a striking phosphaturia, not accompanied by an increase in nephrogenous cAMP excretion. Both free water clearance in Brattleboro rats and free water reabsorption in normal rats was significantly depressed by VO4. These data demonstrate that VO4 depresses tubular reabsorption in proximal and distal nephron segments. We conclude that VO4 exerts its effect on tubular function by inhibition of Na-K-ATPase activity.


1991 ◽  
Vol 260 (1) ◽  
pp. R82-R89
Author(s):  
M. G. Ervin ◽  
R. Castro ◽  
D. J. Sherman ◽  
M. G. Ross ◽  
J. F. Padbury ◽  
...  

Circulating epinephrine alters atrial natriuretic factor (ANF) and arginine vasopressin (AVP) secretion, and all three hormones influence renal function. To quantify the relationships among fetal plasma epinephrine levels, fetal ANF and AVP secretion, and fetal renal function, six chronically catheterized fetal lambs (132 +/- 1 days gestation) received successive 40-min epinephrine infusions (0.1, 0.4, and 1.8 micrograms.min-1.kg-1). The second epinephrine infusion dose evoked significant increases in urine flow (V; 0.7 +/- 0.2 to 1.2 +/- 0.2 ml/min), free water clearance (CH2O; 0.3 +/- 0.1 to 0.7 +/- 0.1 ml/min), glomerular filtration rate (GFR; 3.9 +/- 0.7 to 5.4 +/- 0.8 ml/min), fractional water excretion (V/CH2O; 19 +/- 3 to 25 +/- 2%), mean arterial pressure (MAP; 45 +/- 3 to 51 +/- 4 mmHg), and a 94% increase in plasma ANF levels. A fourfold increase in the infusion dose significantly increased osmolar clearance (0.3 +/- 0.1 to 0.6 +/- 0.1 ml/min), sodium excretion (28 +/- 8 to 53 +/- 13 mueq/min), and plasma AVP levels (2.4 +/- 0.5 to 6.4 +/- 2.4 pg/ml) with no additional effect on V, CH2O, GFR, V/GFR, MAP, or plasma ANF levels. Urine osmolality and fractional sodium excretion did not change in response to epinephrine infusion. Our results demonstrate that epinephrine infusion stimulates fetal ANF secretion and to a lesser extent AVP secretion and significantly influences fetal renal function.


1976 ◽  
Vol 54 (3) ◽  
pp. 209-218 ◽  
Author(s):  
Shyan-Yih Chou ◽  
Paul H. Liebman ◽  
Leon F. Ferder ◽  
Daniel L. Levin ◽  
Roy J. Cacciaguida ◽  
...  

The α-adrenergic blocking agent phenoxybenzamine (PBA) was administered intravenously (10 μg kg−1 min−1) during a steady state water diuresis under pentothal anesthesia to six normal dogs, six dogs with chronic thoracic inferior vena cava constriction and ascites (caval dogs) and seven dogs chronically salt depleted by sodium restriction and furosemide administration. In normal dogs urinary sodium excretion increased significantly from 265 ± 56 (SEM) to 370 ± 65 μequiv./min, whereas no increase in sodium excretion was noted in either caval dogs or salt depleted animals after PBA. In all three groups urine volume, fractional free water clearance and distal sodium load did not change significantly. In normal dogs, distal tubular sodium reabsorption decreased significantly from 73.4 ± 2.8% to 63.1 ± 4.0%, whereas no change was noted in caval or salt depleted dogs. Blood pressure and renal hemodynamics were not significantly altered by PBA administration in any group. These data demonstrate a natriuretic effect of α-adrenergic blockade in normal dogs with the major effect in the water clearing segment of the nephron. The absence of any effect in chronic caval or salt depleted dogs suggests that increased α-adrenergic activity does not play a significant role in the sodium retention of these animals.


1979 ◽  
Vol 56 (2) ◽  
pp. 169-177 ◽  
Author(s):  
S. P. Wilkinson ◽  
T. P. Jowett ◽  
J. D. H. Slater ◽  
V. Arroyo ◽  
H. Moodie ◽  
...  

1. In a group of patients with cirrhosis who showed a wide range of values for the rate of renal sodium excretion, the latter was found to be inversely related to both the plasma concentration and rate of renal excretion of aldosterone. However, for a given sodium excretion the values for aldosterone were significantly lower in the patients than for a group of healthy control subjects. These findings suggest either an increased renal tubular sensitivity to aldosterone or the participation of other factors in the pathogenesis of the sodium retention. 2. Based on measurements of the rate of urine flow and the clearances of free water and inulin during a maximal water diuresis, the fractional reabsorption of sodium by the ‘proximal’, ‘diluting segment’ and ‘distal’ segments of the nephron was estimated. For patients retaining sodium the enhanced reabsorption occurred at both proximal and distal sites, the latter being quantitatively more important. There was no significantly enhanced sodium reabsorption in the diluting segment.


2017 ◽  
Vol 85 (7) ◽  
Author(s):  
Dharmvir S. Jaswal ◽  
Xizhong Cui ◽  
Parizad Torabi-Parizi ◽  
Lernik Ohanjanian ◽  
Hannish Sampath-Kumar ◽  
...  

ABSTRACT Bacillus anthracis edema toxin (ET) consists of protective antigen (PA), necessary for host cell toxin uptake, and edema factor (EF), the toxic moiety which increases host cell cyclic AMP (cAMP). Since vasopressin stimulates renal water and sodium reabsorption via increased tubular cell cAMP levels, we hypothesized the ET would also do so. To test this hypothesis, we employed an isolated perfused rat kidney model. Kidneys were isolated and perfused with modified Krebs-Henseleit buffer. Perfusate and urine samples were obtained at baseline and every 10 min over 150 min following the addition of challenges with or without treatments to the perfusate. In kidneys perfused under constant flow or constant pressure, compared to PA challenge (n = 14 or 15 kidneys, respectively), ET (13 or 15 kidneys, respectively) progressively increased urine cAMP levels, water and sodium reabsorption, and urine osmolality and decreased urine output (P ≤ 0.04, except for sodium reabsorption under constant pressure [P = 0.17]). In ET-challenged kidneys, compared to placebo treatment, adefovir, an EF inhibitor, decreased urine cAMP levels, water and sodium reabsorption, and urine osmolality and increased urine output, while raxibacumab, a PA-directed monoclonal antibody (MAb), decreased urine cAMP levels, free water reabsorption, and urine osmolality and increased urine output (P ≤ 0.03 except for urine output with raxibacumab [P = 0.17]). Upon immunohistochemistry, aquaporin 2 was concentrated along the apical membrane of tubular cells with ET but not PA, and urine aquaporin 2 levels were higher with ET (5.52 ± 1.06 ng/ml versus 1.51 ± 0.44 ng/ml [means ± standard errors of the means {SEM}; P = 0.0001). Edema toxin has renal effects that could contribute to extravascular fluid collection characterizing anthrax infection clinically.


1982 ◽  
Vol 242 (5) ◽  
pp. F491-F498
Author(s):  
A. D. Baines ◽  
B. D. Ross

To examine links between norepinephrine- (NE) stimulated sodium transport and gluconeogenesis, we perfused isolated rat kidneys with 6% albumin, containing various combinations of glucose, alanine, pyruvate. and lactate and inhibitors of gluconeogenesis (0.1 mM mercaptopicolinate, MP) or glucose metabolism (0.2-0.5 mM 2-deoxyglucose, DG). Inulin clearance, fractional potassium reabsorption, total sodium reabsorption, and free water clearance were higher in kidneys perfused with 5 mM glucose plus 2 mM alanine than in kidneys perfused with either 10 mM lactate or 5 mM pyruvate. NE, added after 40 min of perfusion, decreased fractional sodium and potassium excretion in all experiments. In lactate- and/or pyruvate-perfused kidneys NE decreased fractional water excretion with little increase in free water clearance; free water formation was lowest in kidneys perfused with DG or MP. Glucose (5 mM) reversed the inhibitory effect of MP on free water clearance. In glucose-perfused kidneys NE did not decrease fractional water excretion, whereas free water clearance increased threefold. NE stimulated glucose production from pyruvate 2.4-fold and from lactate 1.6-fold. MP inhibited gluconeogenesis both in the basal state and after NE. We conclude that the formation of dilute urine requires nonoxidative glucose metabolism to maintain low water permeability in the diluting segment and a high peritubular glucose concentration that is ensured by gluconeogenesis in adjacent proximal tubules.


1975 ◽  
Vol 228 (5) ◽  
pp. 1525-1530 ◽  
Author(s):  
A Besarab ◽  
P Silva ◽  
B Ross ◽  
FH Epstein

The role of bicarbonate reabsorption and of transtubular chloride gradients in the bulk reabsorption of sodium and water by renal tubules can be tested in the isolated perfused kidney by perfusing with a medium from which bicarbonate has been omitted. Perfusion of the isolated rat kidney with an artificial medium in which bicarbonate is replaced by chloride results in a fall in fractional reabsorption of sodium from 97 to 84%. Stepwise restoration of bicarbonate concentration in the perfusion medium to 25 meq/liter is associated with a parallel recovery of sodium reabsorption to control levels. Inhibition of bicarbonate reabsorption with acetazolamide produces a slightly smaller reduction in sodium reabsorption (97-89%), an effect not seen in the absence of bicarbonate. Acetazolamide greatly increases phosphate excretion and free water clearance in a way consistent with suppression of proximal tubular reabsorption. By contrast, simple omission of bicarbonate from the perfusing medium does not alter phosphaturia or free water clearance. Reabsorption of bicarbonate appears to account for a fraction of sodium reabsorption roughly equivalent to the proportion of sodium associated stoichiometrically with bicarbonate in the glomerule filtrate. The data do not support the hypothesis that the development of a transtubular chloride gradient is critically important for the reabsorption of a large fraction of the glomerular filtrate.


1983 ◽  
Vol 61 (12) ◽  
pp. 1462-1466 ◽  
Author(s):  
A. D. Baines ◽  
A. J. DeBold ◽  
H. Sonnenberg

To examine the mechanisms underlying the natriuretic action of a partially purified extract of rat atria (AE) we injected the equivalent of one atrium into isolated perfused rat kidneys. Some kidneys received an infusion of angiotensin II at 0.5 ng/min throughout the experiment. In the absence of angiotensin AE had a variable effect on renal vascular resistance (RVR) but, in the presence of angiotensin II, AE consistently decreased RVR by 3% for 5 min followed by a slight increase. Inulin clearance and filtration fraction increased slightly but significantly. AE increased sodium, chloride, phosphate, and free water clearance but not potassium excretion. Ventricular extract had no effect on any of these variables. Furosemide (50–250 μg) increased sodium, chloride, and potassium but not phosphate or free water excretion. AE did not alter dopamine or norepinephrine excretion. We conclude that AE increases the glomerular filtration rate (GFR) and inhibits tubular reabsorption by mechanisms which differ, at least in part, from those affected by furosemide.


1975 ◽  
Vol 229 (3) ◽  
pp. 746-753 ◽  
Author(s):  
T Kahn ◽  
J Bosch ◽  
MF Levitt ◽  
MH Goldstein

Effects of sodium nitrate were compared with sodium chloride loading on transport of electrolytes by the nephron. Maximal levels of free water clearance/clomerular filtration rate (CH2O/GFR) averaged 8.4% with nitrate loading and 14.4% with saline loading. Since ethacrynic acid and chlorothiazide exert their major natriuretic effect in the distal nephron, the increment in Na ad Cl reabsorbed beyond the proximal tubule. The administration of these agents resulted in an increase in fractional sodium excretion (CNa/GFR) of 21.1%, urinary sodium excretion (UNaV) of 1,126 mueq/min, and urinary chloride excretion (UClV) of 848 mueq/min during nitrate loading compared with an increase in CNa/GFR of 37.6%, UNaV of 2,362 mueq/min, and UClV of 2,397 mueq/min during saline loading. The smaller diuretic-induced increment in Na and Cl excretion in the nitrate studies suggests, as do the hydrated studies, that less Cl and Na are reabsorbed in the distal nephron during nitrate than saline loading. At every level of UNaV, fractional bicarbonate reabsorption was higher, urine pH was lower, and urinary potassium excretion (UKV) was higher in the nitrate studies. Thus, compared with saline loading, sodium nitrate decreases chloride and sodium reabsorption in the distal nephron. The higher hydrogen and potassium secretion in the nitrate studies may be consequent to the decreased ability of the distal nephron to reabsorb chloride.


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