Renal Vasodilatation: Studies on the Site of Action in the Nephron

1972 ◽  
Vol 42 (5) ◽  
pp. 535-543 ◽  
Author(s):  
S. G. Massry ◽  
J. J. Ahumada
Keyword(s):  
Urine Volume ◽  
Free Water ◽  
Urinary Sodium Excretion ◽  
Sodium Reabsorption ◽  
Water Reabsorption ◽  
Diluting Segment ◽  
Free Water Clearance ◽  
Medullary Blood Flow ◽  
Site Of Action ◽  
Additional Role

1. The effect of unilateral renal vasodilatation produced by acetylcholine or bradykinin on free water clearance (CH2O) and free water reabsorption (TcH2O) was investigated in dogs in an effort to localize the site(s) in the nephron where renal vasodilatation inhibits tubular sodium reabsorption. 2. Renal vasodilatation in dogs undergoing water diuresis produced an increase in urinary sodium excretion, urine volume and CH2O. However, for any given level of sodium delivery to the diluting segment of the nephron, CH2O was less during the intrarenal infusion of the vasodilator drugs than during the infusion of hypo-osmotic saline. 3. During renal vasodilatation in hydropenic dogs receiving vasopressin and hyperosmotic saline, TcH2O at a given rate of osmolal clearance was depressed. The effect of bradykinin on TcH2O was greater than that of acetylcholine. 4. The results indicate that renal vasodilatation inhibits sodium reabsorption in the proximal tubule and the diluting segment of the nephron as well. Increased medullary blood flow may play an additional role in the effect of acetylcholine and bradykinin on TcH2O.

Effects of α-adrenergic blockade on sodium excretion in normal and chronic salt retaining dogs

1976 ◽  
Vol 54 (3) ◽  
pp. 209-218 ◽  
Author(s):  
Shyan-Yih Chou ◽  
Paul H. Liebman ◽  
Leon F. Ferder ◽  
Daniel L. Levin ◽  
Roy J. Cacciaguida ◽  
...  
Keyword(s):  
Sodium Excretion ◽  
Urine Volume ◽  
Vena Cava ◽  
Free Water ◽  
Urinary Sodium Excretion ◽  
Blocking Agent ◽  
Major Effect ◽  
Sodium Reabsorption ◽  
Adrenergic Blockade ◽  
Free Water Clearance

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.

Abstract P166: The Effects of V2 Receptor Antagonist Treatment on the Renal Medullary Circulation and Urinary Sodium Excretion in Rat

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Yusuke Ohsaki ◽  
Takefumi Mori ◽  
Kento Akao ◽  
Yoshimi Nakamichi ◽  
Chika Takahashi ◽  
...  
Keyword(s):  
Blood Flow ◽  
Urine Volume ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
Sodium Reabsorption ◽  
No Production ◽  
Doppler Flowmetry ◽  
Medullary Blood Flow ◽  
V2 Receptor ◽  
Renal Medullary Blood Flow

Objective: V2 receptor (V2R) antagonist increases aquaresis, and was reported to have renoprotective and natriuretic effect, although the mechanism is not fully clarified. Renal medullary hemodynamics contributes sodium retention and renal injury. Therefore, the present study was designed to evaluate the effect of V2R antagonist on renal medullary blood flow. Methods: Catheter was inserted in femoral artery and vein of anesthetized SD rats to monitor blood pressure (BP), heart rate (HR) and to infuse drugs, respectively. Renal medullary blood flow (MBF) and renal medullary oxygen pressure (pO2) were measured with laser-Doppler flowmetry or oxygen microelectrode, respectively. V2R antagonist, OPC-31260 (OPC, 0.25mg/kg bw/h) or furosemide (Furo, 0.5mg/kg bw/h) was intravenously administrated for 90min. Urine was collected in 30 min interval and urinary sodium (UNaV), hydrogen peroxide (UH2O2V) and [nitrate + nitrite] (UNOxV) excretion were measured. Results: OPC and Furo treatment did not change BP and HR. Urine volume was significantly increased by OPC (1.1+0.2 to 6.1+0.5 g/30 min) and Furo (1.4+0.6 to 4.7+0.3 g/30 min) treatment but was not different between groups. MBF was significantly decreased in Furo (12+4% decrease from baseline), while OPC did not changed MBF (1+3% increase from baseline). pO2 was significantly increased by both OPC and Furo treatment (20+6 and 27+10% increase from baseline, respectively). UNaV was significantly increased in OPC (0.10+0.02 to 0.44+0.05 mEq/30 min) and Furo (0.14+0.08 to 0.69+0.06 mEq/30 min) treatment, the increase of UNaV was significantly higher in Furo than OPC group. UH2O2V was significantly increased by Furo treatment (16+4 to 28+6 nmol/30 min), while did not change in OPC treatment (10+2 to 19+4 nmol/30 min). UNOx was significantly increased in OPC treatment (211+30 to 376+45 nmol/30 min), while did not change in Furo treatment (142+27 to 237+75 nmol/30 min). Conclusion: OPC treatment increased NO production. Increased NO could contribute to decrease of sodium reabsorption, result in increase of renal medullary pO2. This scheme could be one on the mechanisms of renal protective effect by V2R antagonist treatment.

Cooperative mechanisms of acute antidiuretic response to bendroflumethiazide in rats with lithium-induced nephrogenic diabetes insipidus

2010 ◽  
Vol 88 (12) ◽  
pp. 1191-1201 ◽  
Author(s):  
S. Mostafa Shid Moosavi ◽  
Masoud Haghani
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Urine Volume ◽  
Free Water ◽  
Urine Flow ◽  
Water Reabsorption ◽  
Free Water Clearance ◽  
Urinary Osmolality ◽  
Antidiuretic Effect ◽  
Water Clearance

The exact mechanism underlying thiazides-induced paradoxical antidiuresis in diabetes insipidus is still elusive, but it has been hypothesized that it is exerted either via Na+-depletion activating volume-homeostatic reflexes to decrease distal delivery, or direct stimulation of distal water reabsorption. This study examined how these two proposed mechanisms actually cooperate to induce an acute bendroflumethiazide (BFTZ)-antidiuretic effect in nephrogenic diabetes insipidus (NDI). Anaesthetized rats with lithium (Li)-induced NDI were prepared in order to measure their renal functional parameters, and in some of them, bilateral renal denervation (DNX) was induced. After a 30 min control clearance period, we infused either BFTZ into 2 groups, NDI+BFTZ and NDI/DNX+BFTZ, or its vehicle into a NDI+V group, and six 30 min experimental clearance periods were taken. During BFTZ infusion in the NDI+BFTZ group, transiently elevated Na+ excretion was associated with rapidly increased urinary osmolality and decreased free water clearance, but Li clearance and urine flow declined in the later periods. However, in the NDI/DNX+BFTZ group, there was persistently elevated Na+ excretion with unchanged Li clearance and urine flow during the experimental period, while alterations in free water clearance and urinary osmolality resembled those in the NDI+BFTZ group. In conclusion, BFTZ initially exerted two direct effects of natriuresis–diuresis and stimulating free water reabsorption at the distal nephron in NDI, which together elevated Na+ excretion and urinary osmolality but kept the urine volume unchanged in the first hour. Thereafter, the resultant sodium depletion led to the activation of neural reflexes that reduced distal fluid delivery to compensate for BFTZ-induced natriuresis–diuresis which, in cooperation with the direct distal BFTZ-antidiuretic effect, resulted in excretion of urine with a low volume, high osmolality, and normal sodium.

Mechanism of natriuresis and diuresis during elevated renal arterial pressure

1965 ◽  
Vol 209 (1) ◽  
pp. 95-99 ◽  
Author(s):  
Ewald E. Selkurt ◽  
Isaac Womack ◽  
William N. Dailey
Keyword(s):  
Arterial Pressure ◽  
Hormonal Regulation ◽  
Urine Volume ◽  
Free Water ◽  
Elevated Pressure ◽  
Sodium Reabsorption ◽  
Osmotic Gradient ◽  
Free Water Clearance ◽  
Sodium Gradient ◽  
Sodium Clearance

Continuous perfusion of the dog's renal artery at pressures averaging 200 mm Hg resulted in natriuresis, increased osmolar clearance, and increase in urine volume. The diuresis was typified by a decrease in TcHH2O, and in some instances positive free water clearance resulted. U/P of osmolality also declined, in some cases below unity. The above changes were observed in the absence of increase in glomerular filtration rate, as measured by creatinine clearance. The reductions in TcHH2O and U/P osmolality were correlated with decrease in the papillary to cortical sodium gradient. Thus, a washout of the osmotic gradient appeared to be the mechanism responsible for the decrease in ability of ADH to concentrate the urine. Because sodium and total osmolar load did not increase during the elevated pressure perfusion, decreased tubular reabsorption must have accounted for the natriuresis and enhanced osmolar clearance. It is speculated that the papillary sodium washout might indirectly influence sodium reabsorption by the ascending limb of the loop of Henle. The possibility is also considered that a mechanism of intrarenal hormonal regulation, responsive to changes in arterial pressure, might be responsible for the increased sodium clearance.

Nonoxidative glucose metabolism a prerequisite for formation of dilute urine

1982 ◽  
Vol 242 (5) ◽  
pp. F491-F498
Author(s):  
A. D. Baines ◽  
B. D. Ross
Keyword(s):  
Glucose Metabolism ◽  
Free Water ◽  
Glucose Production ◽  
Inhibitory Effect ◽  
Sodium Reabsorption ◽  
Diluting Segment ◽  
Free Water Clearance ◽  
Water Excretion ◽  
Total Sodium ◽  
Water Clearance

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.

Effect of sodium nitrate loading on electrolyte transport by the renal tubule

1975 ◽  
Vol 229 (3) ◽  
pp. 746-753 ◽  
Author(s):  
T Kahn ◽  
J Bosch ◽  
MF Levitt ◽  
MH Goldstein
Keyword(s):  
Sodium Nitrate ◽  
Sodium Excretion ◽  
Free Water ◽  
Urinary Sodium Excretion ◽  
Sodium Reabsorption ◽  
Distal Nephron ◽  
Urine Ph ◽  
Free Water Clearance ◽  
Saline Loading ◽  
Urinary Potassium

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.

Natriuresis in Rats Acutely Depleted of Chloride

1977 ◽  
Vol 52 (1) ◽  
pp. 23-31
Author(s):  
R. G. Luke ◽  
B. T. Khanh ◽  
R. D. Schmidt ◽  
J. H. Galla
Keyword(s):  
Sodium Bicarbonate Solution ◽  
Free Water ◽  
Sodium Reabsorption ◽  
Urinary Flow ◽  
Variable Degree ◽  
Water Reabsorption ◽  
Chloride Depletion ◽  
Sodium Load ◽  
Clearance Studies ◽  
And Control

1. Acute chloride depletion, without sodium depletion, was produced in rats by a single exchange peritoneal dialysis against sodium bicarbonate solution. Blood volume was restored after dialysis by infusion of salt-free albumin, and exogenous deoxycorticosterone and antidiuretic hormone were given. 2. Clearance studies in the period (3 h) after dialysis revealed no difference in the glomerular filtration rate or in the filtered sodium load between experimental and control rats but urinary sodium concentrations and absolute and fractional sodium excretion were significantly higher in the chloride-depleted group. 3. There was also a significant kaliuresis, increased urinary flow rate and diminished free water reabsorption. Urinary bicarbonate excretion increased to a variable degree but the major rise in anion excretion was ‘unmeasured’ (Na+ + K+ — [Cl− +HCO3− +PO43-]). 4. It is postulated that chloride depletion imposes limitations on sodium reabsorption in the ascending limb of the loop of Henle.

Effect of sodium fluoride on concentrating and diluting ability in the rat

1977 ◽  
Vol 232 (4) ◽  
pp. F335-F340 ◽  
Author(s):  
J. D. Wallin ◽  
R. A. Kaplan
Keyword(s):  
Cyclic Amp ◽  
Urine Volume ◽  
Free Water ◽  
Urine Osmolality ◽  
Inhibitory Effect ◽  
Sprague Dawley ◽  
Free Water Clearance ◽  
Sprague Dawley Rats ◽  
Direct Inhibitory Effect ◽  
Hereditary Hypothalamic Diabetes Insipidus

Mechanisms for the concentrating defect produced by fluoride were examined in the rat. Free-water clearance at all levels of delivery was normal after 5 days of chronic fluoride administration in the hereditary hypothalamic diabetes insipidus rat. In the Sprague-Dawley rats, during moderate fluoride administration (120 micronmol/kg per day), urine osmolality and cyclic AMP excretion decreased and urine volume increased, but after exogenous vasopressin, volume decreased and osmolality and cyclic AMP increased appropriately. During larger daily doses of fluoride (240 micronmol/kg per day) urinary osmolality and cyclic AMP decreased and volume increased, which was similar to the changes seen during lower fluoride dosages, but these parameters did not change after exogenous vasopressin. These data suggest that ascending limb chloride reabsorption is unaltered by fluoride administration; in the presence of sufficient fluoride, collecting tubular cells apparently do not generate cyclic AMP or increase permeability appropriately in response to vasopressin. The postulated defect is felt to be due to either a decrease in ATP availability or to a direct inhibitory effect of fluoride on the vasopressin-dependent cyclic AMP generating system.

scholarly journals PECULIARITIES OF IONOREGULATORY RENAL FUNCTION OF RATS IN THE DYNAMICS OF EXPERIMENTAL DIABETES MELLITUS DEVELOPMENT WITH UNDERLYING PHARMACOLOGICAL BLOCADE OF RENIN-ANGIOTENSINALDOSTERONE SYSTEM

2021 ◽  
Vol 19 (4) ◽  
Author(s):  
О.А. Olenovych
Keyword(s):  
Diabetes Mellitus ◽  
Renal Function ◽  
Free Water ◽  
Distal Segment ◽  
Male Rats ◽  
Sodium Reabsorption ◽  
Free Water Clearance ◽  
Glomerular Filtrate ◽  
Pharmacological Blockade

The aim of the study – to explore the role of the renin-angiotensin-aldosteronesystem (RAAS) in the disturbance of ionoregulatory renal function in alloxan-inducedexperimental diabetes mellitus (EDM).Material and methods. The experiments were carried out on 78 white non-linearmature male rats with 11-, 26- and 46-day long alloxan-induced EDM with underlyingpharmacological blockade of RAAS by administration of kaptopril. The study ofionoregulating function of the kidneys was provided by the clearance method under thecondition of water 2-hour diuresis.Results. Pharmacological blockade of RAAS in rats with alloxan-induced EDM causedan intensification of natriuresis at all stages of the experiment: increased urinaryconcentration of sodium ions, its excretion and clearance. On the 11th day of EDM, thesodium filtration charge increased with the development of hyponatremia, proximal anddistal sodium reabsorption standardized in volume of glomerular filtrate (GF) decreased,kaliuresis was suppressed, and sodium-free water clearance elevated. In case of 26-daylong EDM, the sodium filtration charge decreased, its absolute and relative reabsorption,the distal sodium reabsorption standardized by GF increased. Kaliuresis increased. In46-day long EDM, the sodium filtration charge decreased, and hyponatremia enhanced.Absolute and relative sodium reabsorption reduced due to both – proximal and distal.Kaliuresis augmented, the clearance of sodium-free water declined.Conclusions. The increase in urinary sodium loss during the 11-day EDM is stipulatedby glomerular hyperfiltration, causing a functional weakening of the tubulotubularbalance and relative dysfunction of the distal segment of the nephron, emphasizing therenoprotective effect of RAAS on ionoregulatory function of the kidneys. The decrease inthe total reabsorption potential of the tubular segment of the nephron in the dynamics ofEDM development reflects on the proximal tubules, and preserved tubulotubular balancecertifies functional intactness of the distal tubules in 26-day long EDM. RAAS pathologicalactivation and attenuation of the renal blood flow autoregulation by tubuloglomerularfeedback may serve as an initiating factor in the development of tubular disorders in 26-day long alloxan diabetes with following progression in 46-day long EDM.

Cardiovascular, renal, and endocrine responses to intravenous endothelin in conscious dogs

1988 ◽  
Vol 255 (6) ◽  
pp. R1064-R1068 ◽  
Author(s):  
K. L. Goetz ◽  
B. C. Wang ◽  
J. B. Madwed ◽  
J. L. Zhu ◽  
R. J. Leadley
Keyword(s):  
Vascular Endothelial Cells ◽  
Peripheral Resistance ◽  
Free Water ◽  
Urine Osmolality ◽  
Urinary Sodium Excretion ◽  
Conscious Dogs ◽  
Plasma Norepinephrine ◽  
Vascular Endothelial ◽  
Free Water Clearance ◽  
Physiological Processes

Endothelin is a recently discovered vasoconstrictor peptide that is synthesized in certain vascular endothelial cells. We have identified the cardiovascular, renal, and hormonal responses that can be elicited in conscious dogs by intravenous administration of endothelin at rates of 10 and 30 ng.kg-1.min-1 for 60 min (0.24 and 0.72 nmol.kg-1/1-h infusion). Each dose of endothelin increased total peripheral resistance, arterial pressure, and left atrial pressure and decreased heart rate and cardiac output. Hematocrit increased by 4.8% (NS) and 22.9% (P less than 0.01) in response to the lower and higher infusion rates, respectively. Urinary sodium excretion, urine osmolality, and osmolar clearance decreased and free water clearance increased. The lower dose of endothelin decreased plasma norepinephrine and increased plasma atriopeptin. The higher dose increased plasma levels of vasopressin, renin, aldosterone, norepinephrine, epinephrine, and atriopeptin. The higher infusion rate of the peptide caused one or more brief vomiting episodes in four of five dogs. Although it is not yet known whether endothelin is a circulating hormone, it is clear that this peptide is capable of causing profound cardiovascular, renal, and endocrine alterations in conscious dogs. The possible relevance of these observations to physiological processes and to pathological conditions such as hypertension remains to be established.

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