scholarly journals Tubule-vascular feedback in renal autoregulation

2019 ◽  
Vol 316 (6) ◽  
pp. F1218-F1226 ◽  
Author(s):  
Cesar A. Romero ◽  
Oscar A. Carretero
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Distal Tubule ◽  
Thick Ascending Limb ◽  
Molecular Signaling ◽  
Feedback Mechanisms ◽  
Salt Diet ◽  
Connecting Tubule ◽  
Main Determinants

Afferent arteriole (Af-Art) diameter regulates pressure and flow into the glomerulus, which are the main determinants of the glomerular filtration rate. Thus, Af-Art resistance is crucial for Na+ filtration. Af-Arts play a role as integrative centers, where systemic and local systems interact to determine the final degree of resistance. The tubule of a single nephron contacts an Af-Art of the same nephron at two locations: in the transition of the thick ascending limb to the distal tubule (macula densa) and again in the connecting tubule. These two sites are the anatomic basis of two intrinsic feedback mechanisms: tubule-glomerular feedback and connecting tubule-glomerular feedback. The cross communications between the tubules and Af-Arts integrate tubular Na+ and water processing with the hemodynamic conditions of the kidneys. Tubule-glomerular feedback provides negative feedback that tends to avoid salt loss, and connecting tubule-glomerular feedback provides positive feedback that favors salt excretion by modulating tubule-glomerular feedback (resetting it) and increasing glomerular filtration rate. These feedback mechanisms are also exposed to systemic modulators (hormones and the nervous system); however, they can work in isolated kidneys or nephrons. The exaggerated activation or absence of any of these mechanisms may lead to disequilibrium in salt and water homeostasis, especially in extreme conditions (e.g., high-salt diet/low-salt diet) and may be part of the pathogenesis of some diseases. In this review, we focus on molecular signaling, feedback interactions, and the physiological roles of these two feedback mechanisms.

Effects of blood pH changes on potassium excretion in the dog

1962 ◽  
Vol 202 (4) ◽  
pp. 768-772 ◽  
Author(s):  
Charles Toussaint ◽  
Pierre Vereerstraeten
Keyword(s):  
Glomerular Filtration Rate ◽  
Proximal Tubule ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Excretion Rate ◽  
Distal Tubule ◽  
Potassium Excretion ◽  
Ph Changes ◽  
Blood Ph ◽  
Ph Level

K+ excretion rate was measured at normal as well as at rising plasma K+ concentration in intact, in K-depleted, and in acetazolamide-treated dogs submitted to acute blood pH changes. The results indicate that, for any given value of glomerular filtration rate, K+ excretion rate is determined by at least three factors: 1) plasma K+ concentration, 2) blood pH level, and 3) presumably, the H+ gradient across the luminal border of the distal tubule. The data further suggest that most of the filtered K+ is reabsorbed by the proximal tubule, even in conditions of high filtered loads.

Micropuncture study of the superficial nephron of Perognathus penicillatus

1981 ◽  
Vol 241 (6) ◽  
pp. F612-F617
Author(s):  
E. J. Braun ◽  
D. R. Roy ◽  
R. L. Jamison
Keyword(s):  
Glomerular Filtration Rate ◽  
Proximal Tubule ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Distal Tubule ◽  
Urine Osmolality ◽  
Small Rodent ◽  
Micropuncture Study ◽  
Single Nephron ◽  
Average Body

A micropuncture study of Perognathus penicillatus, a small rodent native to the deserts of the southwestern United States was performed to evaluate the function of the superficial nephron. Data are reported for 12 animals of 17 g average body wt. Mean glomerular filtration rate was 475 +/- 73 microliter X min-1 X g kidney wt-1. Urine osmolality averaged 1,154 +/- 197 mosmol/kg H2O. Single nephron glomerular filtration rate averaged 43 nl X min-1 X g kidney wt-1 in the proximal tubule and 48 in the distal tubule, values that are not significantly different. In terms of the filtered load remaining unreabsorbed at the end of the accessible proximal tubule, the average percentages were 46 water, 48 total solute, 45 sodium, 56 phosphorus, 62 potassium, 71 magnesium, and 54 calcium. The concentrations of potassium and magnesium in fluid samples increased significantly along the proximal tubule. Approximately at the midpoint of the distal tubule, fractional delivery of water, 13.1%, was greater than that for total solute, 10%, or sodium, 7%, indicating that the intervening segment of nephron reabsorbed solute and sodium in excess of water. The function of the superficial nephron resembles that of species previously investigated except for potassium reabsorption in the proximal convoluted tubule.

Cisplatin nephrotoxicity in rats: defect in papillary hypertonicity

1981 ◽  
Vol 241 (2) ◽  
pp. F175-F185 ◽  
Author(s):  
R. Safirstein ◽  
P. Miller ◽  
S. Dikman ◽  
N. Lyman ◽  
C. Shapiro
Keyword(s):  
Glomerular Filtration Rate ◽  
Proximal Tubule ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Collecting Duct ◽  
Urine Volume ◽  
Distal Tubule ◽  
Urine Osmolality ◽  
Solute Content ◽  
Cisplatin Nephrotoxicity

We examined the effects of cisplatin (5 mg/kg BW) on renal function in rats. Three days after administration of cisplatin whole kidney clearance of inulin fell and 24-h urine volume increased. Maximal urine osmolality and papillary solute content were reduced. Superficial nephron glomerular filtration rate measured along the proximal tubule, where no leak of inulin could be demonstrated, was reduced in cisplatin-treated animals. Differences between superficial nephron glomerular filtration rate determined in proximal and distal tubules were greater in cisplatin-treated rats than in control rats. Neither a change in fluid or sodium movement along superficial nephrons nor a reduced early distal tubule transepithelial sodium gradient explain the polyuria. Urea was reabsorbed from, not added to, the loop fluid in cisplatin-treated animals. Morphologic changes were evident in the S3 segment of the proximal tubule in cisplatin-treated animals but the glomeruli were normal. Polyuria occurred despite diminished glomerular filtration rate in cisplatin nephrotoxicity. The diminished concentration of salt and urea in the papilla as a result of abnormal function of the collecting duct or pars recta portion of the proximal tubule contributed to the defect in concentrating ability.

GFR regulation and flow-dependent electrophysiology of early distal tubule in Amphiuma

1987 ◽  
Vol 253 (2) ◽  
pp. F263-F268 ◽  
Author(s):  
B. E. Persson ◽  
D. J. Marsh
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Distal Tubule ◽  
Potential Difference ◽  
Tubuloglomerular Feedback ◽  
Perfusion Rate ◽  
Intracellular Chloride ◽  
Concentration Changes ◽  
Chloride Concentrations

Tubuloglomerular feedback (TGF) in mammals and amphibians senses flow-dependent concentration changes in tubular fluid of the distal tubule and signals to arterioles to initiate changes in glomerular filtration rate. The distal tubules and afferent arterioles are situated on the surface of the kidney of Amphiuma means. Micropuncture techniques were used to measure luminal and intracellular chloride concentrations and the associated electrical potential differences, while tubular perfusion rate was varied. Transepithelial potential difference (PDte) and basolateral potential difference (PDbl) became more positive at increased tubular flow rates. Intratubular and intracellular chloride concentrations also increased significantly with perfusion rate. Single-nephron glomerular filtration rate decreased when perfusion rate was increased but this response was eliminated by the inclusion of furosemide in the perfusion solution; the drug also inhibited the flow dependence of PDte. The results suggest that local changes in PD and Cl- activity result from flow-dependent changes in the rate of hypertonic NaCl transport propagated along the length of the perfused segment; they establish a correlation between the rate of transport and the magnitude of the TGF inhibition; and, because transport and TGF can be jointly inhibited, they suggest a causal link between the two.

Localization of alpha 2-adrenoceptor-mediated increase in renal Na+, K+, and water excretion

1987 ◽  
Vol 252 (6) ◽  
pp. F1016-F1021 ◽  
Author(s):  
B. Stanton ◽  
E. Puglisi ◽  
M. Gellai
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Water Transport ◽  
Filtration Rate ◽  
Distal Tubule ◽  
Fractional Excretion ◽  
Urine Osmolality ◽  
Water Excretion ◽  
Arterial Blood ◽  
Adrenoceptor Agonist

Free-flow micropuncture and clearance studies were conducted in male Sprague-Dawley rats to investigate the effects of alpha 2-adrenoceptor stimulation on Na+, K+, and water transport along the nephron. Intravenous infusion of the selective alpha 2-adrenoceptor agonist B-HT 933 at 1 mg X kg-1 X h-1 increased urinary flow rate from 16.2 +/- 3.6 to 84.8 +/- 11.9 microliter/min, fractional excretion of Na+ from 1.36 +/- 0.31 to 3.57 +/- 0.52%, and fractional excretion of K+ from 26.9 +/- 3.0 to 42.3 +/- 2.2%, The diuresis, saluresis, and kaliuresis were not the result of increases in glomerular filtration rate or mean arterial blood pressure. Urine osmolality decreased from 1,126 +/- 177 to 325 +/- 33 mosmol/kg water and in 8 of the 11 animals studied B-HT 933 decreased urine osmolality to hyposmotic levels, suggesting a possible interaction between the alpha 2-adrenoceptor agonist and vasopressin. The alpha 2-adrenoceptor antagonist yohimbine (0.25/mg bolus, iv) inhibited the diuresis, saliuresis, and kaliuresis. In micropuncture studies, B-HT 933 was without effect on single-nephron glomerular filtration rate or on Na+, K+, and water transport along the superficial proximal tubule, loop of Henle, or distal tubule. Thus stimulation of alpha 2-adrenoceptors increases Na+, K+, and water excretion by inhibiting tubule reabsorption of these substances at nephron sites beyond the superficial distal tubule, most likely by the collecting tubule.

The Paradox of Renal Bicarbonate Reabsorption

Physiology ◽  
1990 ◽  
Vol 5 (1) ◽  
pp. 13-17
Author(s):  
F Kiil
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Bicarbonate Reabsorption ◽  
Main Determinants

A time-honored paradox of renal bicarbonate reabsorption can be understood by realizing that filtered bicarbonate rather than glomerular filtration rate and plasma pH rather than PCO2 are the main determinants of bicarbonate reabsorption.

scholarly journals Maternal protein restriction leads to hyperresponsiveness to stress and salt-sensitive hypertension in male offspring

2010 ◽  
Vol 298 (5) ◽  
pp. R1375-R1382 ◽  
Author(s):  
Robert A. Augustyniak ◽  
Karan Singh ◽  
Daniel Zeldes ◽  
Melissa Singh ◽  
Noreen F. Rossi
Keyword(s):  
Blood Pressure ◽  
Glomerular Filtration Rate ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Low Protein

Low birth weight humans often exhibit hypertension during adulthood. Studying the offspring of rat dams fed a maternal low-protein diet is one model frequently used to study the mechanisms of low birth weight-related hypertension. It remains unclear whether this model replicates key clinical findings of hypertension and increased blood pressure responsiveness to stress or high-salt diet. We measured blood pressure via radiotelemetry in 13-wk-old male offspring of maternal normal- and low-protein dams. Neither group exhibited hypertension at baseline; however, 1 h of restraint was accompanied by a significantly greater blood pressure response in low-protein compared with normal-protein offspring. To enhance the effect of a high-salt diet on blood pressure, normal- and low-protein offspring underwent right uninephrectomy, while controls underwent sham surgery. After 5 weeks on a high-salt diet (4% NaCl), mean arterial pressure in the Low-Protein+Sham offspring was elevated by 6 ± 2 mmHg ( P < 0.05 vs. baseline), while it remained unchanged in the normal-protein offspring. In the two uninephrectomized groups, blood pressure increased further, but was of similar magnitude. Glomerular filtration rate in the low-protein uninephrectomized offspring was 50% less than that in normal-protein offspring with intact kidneys. These data indicate that, while male low-protein offspring are not hypertensive during young adulthood, their blood pressure is hyperresponsive to restraint stress and is salt sensitive, and their glomerular filtration rate is more sensitive to hypertension-causing insults. Collectively, these may predispose for the development of hypertension later in life.

MO652EFFECT OF ESTIMATED GLOMERULAR FILTRATION RATE (EGFR) ON  HEMOGLOBIN CHANGE INDUCED BY SODIUM-GLUCOSE COTRANSPORTER 2  INHIBITORS (SGLT2I)

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Alba Maroto ◽  
Ester Domenech ◽  
Maria Marques Vidas ◽  
Paula López ◽  
Jose' M Portoles
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Multivariate Analysis ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Sglt2 Inhibitors ◽  
Sodium Glucose Cotransporter ◽  
Main Determinants

Abstract Background and Aims The use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) is associated with increase of hemoglobin (Hb) levels and this effect has been related to improvement of tubulointerstitial hypoxia and increase on EPO production. Chronic kidney disease (CKD) associated anemia is mainly due to decreased EPO synthesis. The aim of this study was to assess if the degree of Hb increase induced by SGLT2i is higher on T2DM patients with decreased estimated glomerular filtration rate (eGFR). Method We analyzed the changes on Hb after 12 months of SGLT2i treatment in T2DM patients with different degrees of eGFR. All patients were on maximum tolerated RAA system blockade, and none was on erythropoiesis or iron therapy. Results 62 patients were include, age 67,6 ± 12,3 years, 72.6% males, eGFR CKD EPI 62,9 ± 21 (21-108) ml/min/1.73m2. Type of SGLT2i was dapagliflozin (46.8%), canagliflozin (30,5%) and empagliflozin (22,6%). 7 patients discontinued SGLT2i therapy and 62 were finally include in the analysis. Treatment with SGLT2i induced increase of Hb levels ( ΛHb 0,57 mg/dl SE 0,17 95% CI 0,25-0,93, p 0,001) independently of eGFR (aR2 0.02 p ns) In the multivariate analysis, initial eGFR, and basal Hb were the main determinants of the Hb increase induced by SGLT2i treatment (aR2 0,29). eGFR (≤60 vs &gt;60 ml/min/173) or type of SGLT2i did not modified ΛHb Conclusion We conclude that SGLT2 inhibitors induce increase on Hb level independently of eGFR, in patients with preserved renal function, by mechanisms that are yet to be determined.

Renal autoregulation: perspectives from whole kidney and single nephron studies

1978 ◽  
Vol 234 (5) ◽  
pp. F357-F370 ◽  
Author(s):  
L. G. Navar
Keyword(s):  
Glomerular Filtration Rate ◽  
Arterial Pressure ◽  
Glomerular Filtration ◽  
Vascular Resistance ◽  
Filtration Rate ◽  
Distal Tubule ◽  
Distal Nephron ◽  
Renal Autoregulation ◽  
Single Nephron ◽  
Renal Vascular

The phenomenon of renal autoregulation is often thought to relate only to the manner in which the kidney responds to changes in arterial pressure. This review presents a more comprehensive description of the process based on the intrinsic renal vascular responses to changes in arterial pressure, venous pressure, ureteral pressure, and plasma colloid osmotic pressure. Regulation of glomerular filtration rate (GFR), or some function thereof, is the feature most consistently observed. More specifically, in response to external manipulations that change GFR, autonomous changes in renal vascular resistance tend to return GFR back towards normal. The bulk of the evidence suggests that the requisite renal vascular resistance alterations occur predominately at preglomerular segments. Most of the whole kidney autoregulatory responses can be explained on the basis of the distal tubule-glomerular feedback hypothesis, thought to be mediated by the macula densa-juxtaglomerular complex, which states that increases in distal volume delivery lead to increases in afferent arteriolar resistance while reduced distal delivery leads to afferent arteriolar dilation. Micropuncture data have demonstrated that interruption of distal volume delivery prevents single nephrons from autoregulating GFR and glomerular pressure. Also, single nephron glomerular filtration rate (SNGFR) based on proximal collections is higher than SNGFR measured by distal collections or with an indicator-dilution technique. Studies utilized direct microperfusion of the distal nephron from a late proximal tubule site have demonstrated that SNGFR and glomerular pressure decrease in response to increases in distal nephron perfusion rate. Although experiments in rats have been interpreted as indicating that distal chloride concentration and/or reabsorption most likely mediate the feedback responses, recent studies in dogs have demonstrated that feedback responses can be consistently obtained with nonelectrolyte perfusion solutions. These latter studies suggest that the feedback response may be sensitive to some function of total solute delivery or concentration. At present, there is no clear understanding of the intracellular events that link the compositional alterations occurring within the early distal tubule to the final effector system.

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