Intratubular application of sodium azide inhibits loop of Henle reabsorption and tubuloglomerular feedback response in anesthetized rats

1998 ◽  
Vol 358 (3) ◽  
pp. 367-373 ◽  
Author(s):  
Dan Y. Huang ◽  
Hartmut Osswald ◽  
V. Vallon
Keyword(s):  
Sodium Azide ◽  
Tubuloglomerular Feedback ◽  
Loop Of Henle ◽  
Anesthetized Rats

Depolarization of the macula densa induces superoxide production via NAD(P)H oxidase

2007 ◽  
Vol 292 (6) ◽  
pp. F1867-F1872 ◽  
Author(s):  
Ruisheng Liu ◽  
Jeffrey L. Garvin ◽  
YiLin Ren ◽  
Patrick J. Pagano ◽  
Oscar A. Carretero
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Oxidase Inhibitor ◽  
Fluorescent Dye ◽  
Macula Densa ◽  
Superoxide Production ◽  
Tubuloglomerular Feedback ◽  
Thick Ascending Limb ◽  
Loop Of Henle ◽  
Nacl Concentration

Superoxide (O2−) enhances tubuloglomerular feedback by scavenging nitric oxide at the macula densa. However, the singling pathway of O2− production in the macula densa is not known. We hypothesized that the increase in tubular NaCl concentration that initiates tubuloglomerular feedback induces O2− production by the macula densa via NAD(P)H oxidase, which is activated by macula densa depolarization. We isolated and microperfused the thick ascending limb of the loop of Henle and attached macula densa in rabbits. A fluorescent dye, dihydroethidium, was used to detect O2− production at the macula densa. When luminal NaCl was switched from 10 to 80 mM, a situation of initiating maximum tubuloglomerular feedback response, O2− production significantly increased. To make sure that the shifts in the oxyethidium/dihydroethidium ratio were due to changes in O2−, we used tempol (10−4 M), a stable membrane-permeant superoxide dismutase mimetic. With tempol present, when we switched from 10 to 80 mM NaCl, the increase in oxyethidium/dihydroethidium ratio was blocked. To determine the source of O2−, we used the NAD(P)H oxidase inhibitor apocynin. When luminal NaCl was switched from 10 to 80 mM in the presence of apocynin, O2− production was inhibited by 80%. To see whether the effect of increasing luminal NaCl involves Na-K-2Cl cotransporters, we inhibited them with furosemide. When luminal NaCl was switched from 10 to 80 mM in the presence of furosemide, O2− production was blocked. To test whether depolarization of the macula densa induces O2− production, we artificially induced depolarization by adding valinomycin (10−6 M) and 25 mM KCl to the luminal perfusate. Depolarization alone significantly increases O2− production. We conclude that increasing luminal NaCl induces O2− production during tubuloglomerular feedback. O2− generated by the macula densa is primarily derived from NAD(P)H oxidase and is induced by depolarization.

Renal effects of endogenous prostaglandin synthesis promoter ONO-3122

1992 ◽  
Vol 262 (6) ◽  
pp. F1047-F1054
Author(s):  
T. Takabatake ◽  
H. Hara ◽  
Y. Ishida ◽  
H. Ohta ◽  
K. Kobayashi
Keyword(s):  
Proximal Tubule ◽  
Prostaglandin Synthesis ◽  
Fluid Replacement ◽  
Tubuloglomerular Feedback ◽  
Loop Of Henle ◽  
Distal Nephron ◽  
Water Reabsorption ◽  
Renal Vasculature ◽  
Renal Effects ◽  
Collecting Tubules

The renal effects of a prostaglandin synthesis agonist, 1-iodo-3-aminomethyl-5,6,7,8-tetrahydro-2-naphthol (ONO-3122), were investigated in anesthetized rats. ONO-3122 (0.3 mg/kg + 0.3 mg.kg-1.h-1 iv) doubled the urinary excretion of the main metabolites of prostaglandin F, and induced transient increases in renal blood flow and glomerular filtration rate (GFR) with a marked, stable natriuresis. Indomethacin suppressed the natriuresis. When the diuretic fluid losses were replaced, micropuncture showed an unaltered reabsorption of sodium in the proximal tubule but reductions in the loop of Henle (86 +/- 1 vs. 76 +/- 1%) and in the more distal segments (98 +/- 1 vs. 83 +/- 3%) with comparable reductions in water reabsorption. Potassium secretion was seen in the distal and collecting tubules. Without fluid replacement, sodium reabsorption was reduced in the loop and more distal nephron but increased in the proximal tubule. Differences between proximal and distal nephron GFR were unaffected by systemic ONO-3122. Loop perfusion with ONO-3122 did not change tubuloglomerular feedback responses, which were, however, completely suppressed by furosemide. It is concluded that ONO-3122 stimulates renal prostaglandin biosynthesis, transiently dilates renal vasculature, and induces natriuresis mainly by suppressing sodium and water reabsorption in the loop of Henle and the more distal nephron. Luminal ONO-3122 does not affect the tubuloglomerular feedback.

Micropuncture study of renal tubular reabsorption of calcium in normal rodents

1963 ◽  
Vol 204 (5) ◽  
pp. 771-775 ◽  
Author(s):  
William E. Lassiter ◽  
Carl W. Gottschalk ◽  
Margaret Mylle
Keyword(s):  
Proximal Tubule ◽  
Active Transport ◽  
Tubular Reabsorption ◽  
Loop Of Henle ◽  
Anesthetized Rats ◽  
Micropuncture Study ◽  
Calcium Reabsorption ◽  
Renal Tubular Reabsorption ◽  
Renal Tubular ◽  
Distal Convolution

Anesthetized rats and hamsters were given Ca45 intravenously, and fluid was subsequently collected by micropuncture from glomeruli and surface tubules in the rats, and from loops of Henle in the hamsters. In nondiuretic animals, fluid:plasma calcium ratios averaged 0.71 in the glomerulus; 0.76 in the proximal tubule; 2.0 in the loop of Henle; 0.47 in the distal convolution; and 0.9 in ureteral urine. In mannitol diuresis, the calcium ratio of glomerular fluid was unchanged, but ratios as low as 0.21 were noted in the proximal tubule. In this circumstance, the average proximal ratio was 0.61, and the distal ratio 0.07. These results indicate active transport of calcium out of all major parts of the nephron, with the bulk of calcium reabsorption occurring in the convoluted portion of the proximal tubule. Furthermore, the pattern of tubular reabsorption of calcium is similar to that of sodium, suggesting that the two are related.

Evidence for tubuloglomerular feedback in juxtamedullary nephrons of young rats

1983 ◽  
Vol 244 (4) ◽  
pp. F425-F431 ◽  
Author(s):  
R. Muller-Suur ◽  
H. R. Ulfendahl ◽  
A. E. Persson
Keyword(s):  
Filtration Rate ◽  
Proximal Tubules ◽  
Tubuloglomerular Feedback ◽  
Loop Of Henle ◽  
Perfusion Rate ◽  
Flow Rates ◽  
Young Rats ◽  
Flow Pressure ◽  
Tubular Flow ◽  
Stop Flow

To determine whether the filtration rate of juxtamedullary nephrons is regulated by tubuloglomerular feedback (TGF), we developed two micropuncture techniques suitable for the papilla of young rats. One consisted of measuring the tubular flow in descending limbs of Henle loops (VDLH) while the ascending limbs of the loop of Henle (ALH) were perfused at various rates with three different solutions: modified Ringer, artificial Henle loop solution, and Ringer containing 10(-4) M furosemide. SNGFR was also measured in several juxtamedullary nephrons. The other protocol consisted of measuring the tubular stop-flow pressure (PSF) in descending limbs of the loop of Henle upstream to a wax block. Distal to the block Ringer was perfused at various rates through ALH. Our results provide the first evidence of a TGF response in juxtamedullary nephrons. VDLH and SNGFR decreased during Ringer perfusion to 42 +/- 4 and 44 +/- 4% of their values at zero perfusion. The same pattern was observed using Henle loop solution as perfusate, whereas with furosemide VDLH did not change. The maximal decrease in PSF was 14.1 +/- 1.4 mmHg. The perfusion rate necessary to induce a half-maximal PSF decrease was 9.1 +/- 0.9 nl/min. Similar micropuncture techniques were used in proximal tubules of surface nephrons in these rats, which in comparison to the deep nephrons showed smaller feedback responses. The mechanism seems to be active at physiological nephron flow rates in both nephron populations. Thus, TGF can exert its effect on GFR of the whole kidney by acting in both deep and surface nephrons.

Localization of urine acidification in the mammalian kidney

1960 ◽  
Vol 198 (3) ◽  
pp. 581-585 ◽  
Author(s):  
Carl W. Gottschalk ◽  
William E. Lassiter ◽  
Margaret Mylle
Keyword(s):  
Ammonium Chloride ◽  
Renal Tubules ◽  
Loop Of Henle ◽  
Mammalian Kidney ◽  
Urine Acidification ◽  
Arterial Blood ◽  
Anesthetized Rats ◽  
Collecting Ducts ◽  
Distal Convolution ◽  
Quantitative Importance

Fluid was collected by micropuncture from individual renal tubules of anesthetized rats and its pH determined with the quinhydrone microelectrode. The single glomerular sample and early proximal fluid were isohydric with arterial blood, but later proximal fluid usually showed progressive acidification. The maximum proximal fall in pH was 0.43 u in nondiuretic rats, 0.56 u during profuse glucose or mannitol diuresis, and 0.78 u in rats previously loaded with ammonium chloride and undergoing glucose diuresis. Fluid from the early distal convolution was usually acidified relative to arterial blood but was not significantly different from late proximal fluid. Progressive acidification probably also occurred in the distal convolution. The pH decreased further in the collecting ducts, much more so in the nondiuretic state than during diuresis. The quantitative importance of proximal reabsorption of HCO3– and, by inference, H+ secretion is emphasized. It is suggested that the pH of tubular fluid may increase in the thin descending limb of the loop of Henle, especially in a kidney elaborating a concentrated urine, because of increased concentration of HCO3–.

scholarly journals Renal afferent arteriolar and tubuloglomerular feedback reactivity in mice with conditional deletions of adenosine 1 receptors

2012 ◽  
Vol 303 (8) ◽  
pp. F1166-F1175 ◽  
Author(s):  
Lingli Li ◽  
En Yin Lai ◽  
Yuning Huang ◽  
Christoph Eisner ◽  
Diane Mizel ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Mesangial Cells ◽  
Smooth Muscle Actin ◽  
Critical Role ◽  
Muscle Cells ◽  
Tubuloglomerular Feedback ◽  
Loop Of Henle ◽  
Actin Promoter

Adenosine 1 receptors (A1AR) have been shown in previous experiments to play a major role in the tubuloglomerular feedback (TGF) constrictor response of afferent arterioles (AA) to increased loop of Henle flow. Overexpression studies have pointed to a critical role of vascular A1AR, but it has remained unclear whether selective deletion of A1AR from smooth muscle cells is sufficient to abolish TGF responsiveness. To address this question, we have determined TGF response magnitude in mice in which vascular A1AR deletion was achieved using the loxP recombination approach with cre recombinase being controlled by a smooth muscle actin promoter (SmCre/A1ARff). Effective vascular deletion of A1AR was affirmed by absence of vasoconstrictor responses to adenosine or cyclohexyl adenosine (CHA) in microperfused AA. Elevation of loop of Henle flow from 0 to 30 nl/min caused a 22.1 ± 3.1% reduction of stop flow pressure in control mice and of 7.2 ± 1.5% in SmCre/A1ARff mice ( P < 0.001). Maintenance of residual TGF activity despite absence of A1AR-mediated responses in AA suggests participation of extravascular A1AR in TGF. Support for this notion comes from the observation that deletion of A1ARff by nestin-driven cre causes an identical TGF response reduction (7.3 ± 2.4% in NestinCre/A1ARff vs. 20.3 ± 2.7% in controls), whereas AA responsiveness was reduced but not abolished. A1AR on AA smooth muscle cells are primarily responsible for TGF activation, but A1AR on extravascular cells, perhaps mesangial cells, appear to contribute to the TGF response.

Effect of P-450 omega-hydroxylase metabolites of arachidonic acid on tubuloglomerular feedback

1994 ◽  
Vol 266 (6) ◽  
pp. F934-F941 ◽  
Author(s):  
A. P. Zou ◽  
J. D. Imig ◽  
P. R. Ortiz de Montellano ◽  
Z. Sui ◽  
J. R. Falck ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Tubuloglomerular Feedback ◽  
Loop Of Henle ◽  
Rate Dependent ◽  
Nephron Segment ◽  
Flow Pressure ◽  
Renal Vascular ◽  
Stop Flow ◽  
Renal Vascular Tone

The role of endogenous P-450 metabolites of arachidonic acid (AA) on the tubuloglomerular feedback (TGF) response was examined. Under control conditions stop-flow pressure (SFP) fell by 17.0 +/- 2.1 mmHg when the perfusion rate of the loop of Henle was increased from 0 to 50 nl/min. Addition of AA (50 microM) to the perfusate lowered basal SFP by 11.4 +/- 1.1 mmHg and potentiated the TGF response. This effect was blocked by addition of a P-450 inhibitor, 17-octadecynoic acid (17-ODYA) (10 microM), to the perfusate. Perfusion of the loop of Henle with 17-ODYA elevated basal SFP by 3.7 +/- 0.3 mmHg and reduced the TGF response by 80%. After blockade of endogenous P-450 activity with 17-ODYA, addition of 20-hydroxyeicosatetraenoic acid (20-HETE, 10 microM) to the perfusate produced a flow rate-dependent fall in SFP. The effect of 20-HETE was not altered by pretreating the animal with meclofenamate (2 mg/kg iv) or by perfusing the nephron segment with furosemide (50 microM). These results indicate that endogenous P-450 metabolites of AA, particularly 20-HETE, may play a role in TGF and the regulation of renal vascular tone.

scholarly journals Renal Nerve Deafferentation Attenuates the Fall in GFR during Intravenous Infusion of Furosemide in Anesthetized Rats

2020 ◽  
Vol 45 (1) ◽  
pp. 70-83 ◽  
Author(s):  
Magali Araujo ◽  
Glenn Solis ◽  
William J. Welch ◽  
Christopher S. Wilcox
Keyword(s):  
Proximal Tubule ◽  
Volume Replacement ◽  
Tubuloglomerular Feedback ◽  
Renal Nerves ◽  
Volume Depletion ◽  
Renal Nerve ◽  
At1 Receptors ◽  
Anesthetized Rats ◽  
Renal Nerve Activity ◽  
Renal Vascular

Introduction: Furosemide reduces the glomerular filtration rate (GFR) and increases the renal vascular resistance (RVR) despite inhibiting tubuloglomerular feedback but increases proximal tubule pressure, renin release, and renal nerve activity. Objective: This study tested the hypothesis that the fall in GFR with furosemide is due to volume depletion or activation of angiotensin type 1 (AT1) receptors or renal nerves. Methods: Furosemide was infused for 60 min at 1.0 mg·kg−1·h−1 in groups of 5–8 anesthetized rats. Additional groups received intravenous volume replacement to prevent fluid and Na+ losses or volume replacement plus losartan or plus sham denervation or plus renal denervation or renal nerve deafferentation. Results: At 60 min of infusion, furosemide alone reduced the GFR (–37 ± 4%; p < 0.01). This fall was not prevented by volume replacement or pretreatment with losartan, although losartan moderated the increase in RVR with furosemide (+44 ± 3 vs. +82 ± 7%; p < 0.01). Whereas the GFR fell after furosemide in rats after sham procedure (–31 ± 2%), it was not changed significantly after prior renal deafferentation. Proximal tubule pressure increased significantly but returned towards baseline over 60 min of furosemide, while urine output remained elevated, and GFR and renal blood flow depressed. Conclusions: The fall in GFR over 60 min of furosemide infusion is independent of volume depletion or activation of AT1 receptors but is largely dependent on renal afferent nerves.

Quantitative characterization of the tubuloglomerular feedback response: effect of growth

1984 ◽  
Vol 247 (5) ◽  
pp. F808-F815 ◽  
Author(s):  
J. P. Briggs ◽  
G. Schubert ◽  
J. Schnermann
Keyword(s):  
Flow Rate ◽  
Tubuloglomerular Feedback ◽  
Loop Of Henle ◽  
Sprague Dawley ◽  
Maximum Slope ◽  
Sprague Dawley Rats ◽  
Single Nephron ◽  
Renal Micropuncture ◽  
The Right

Studies were performed to characterize quantitatively the effect of changing loop of Henle flow rate on single nephron glomerular filtration rate (SNGFR) in male Sprague-Dawley rats of varying body weight. Rats weighing 100, 220, and 350 g were studied using standard renal micropuncture techniques. The relationship between loop of Henle flow rate (VLP) and SNGFR was characterized for individual nephrons by multiple determinations of SNGFR during loop perfusion. An inverse sigmoidal relationship was observed that could be described as delta SNGFR = a/(1 + ek(b-VLP], where delta SNGFR is the change in SNGFR from the value measured at zero loop flow, a is delta SNGFRmax, the maximum change, b is V1/2, the flow rate at which the response is half maximum, and k is [4f' (V1/2)]/a with f' (V1/2) the slope at V1/2. delta SNGFRmax increased with increasing body size (7.9 +/- 1.16, 18.9 +/- 0.90, and 25.2 +/- 2.73 nl/min, respectively, in the three groups), and the curve shifted to the right (V1/2 = 10.3 +/- 0.8, 15.4 +/- 0.83, and 22.3 +/- 1.22 nl/min). The maximum slope increased (f' (V1/2) = 0.9 +/- 0.19, 1.7 +/- 0.16, and 3.2 +/- 0.70), but the exponential constant k was uninfluenced by growth. Independent of rat size, a 10% increase in loop flow at the midpoint produced at 5-10% decrease in SNGFR. Free-flow values of SNGFR and VLP were found to lie in the most sensitive range of the feedback curve.

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