The Dependency of the Renin Activity of the Single Juxtaglomerular Apparatus upon Tubular Fluid Composition in the Macula Densa Segment of the Rat Kidney1

2015 ◽  
pp. 291-298
Author(s):  
K. Thurau ◽  
H. Dahlheim ◽  
June Mason ◽  
A. Gr�ner
Keyword(s):  
Juxtaglomerular Apparatus ◽  
Macula Densa ◽  
Renin Activity ◽  
Fluid Composition

Role of macula densa cyclooxygenase-2 in renovascular hypertension

2003 ◽  
Vol 284 (3) ◽  
pp. F498-F502 ◽  
Author(s):  
Andrea Hartner ◽  
Nada Cordasic ◽  
Margarete Goppelt-Struebe ◽  
Roland Veelken ◽  
Karl F. Hilgers
Keyword(s):  
Plasma Renin Activity ◽  
Renovascular Hypertension ◽  
Plasma Renin ◽  
Juxtaglomerular Apparatus ◽  
Macula Densa ◽  
Renin Activity ◽  
Disease States ◽  
Renin Synthesis ◽  
Cox 2

Upregulation of the inducible cyclooxygenase (COX-2) in the macula densa accompanies the activation of the juxtaglomerular apparatus in many high-renin conditions. The functional role of COX-2 in these disease states is poorly understood. We tested whether COX-2 is required to increase renin in renovascular hypertension. Rats with established two-kidney, one-clip (2K1C) hypertension were treated for 2 wk with two different inhibitors of COX-2, NS-398 and rofecoxib, respectively. Hypertension in 2K1C rats was not affected or slightly enhanced by COX-2 inhibition, as measured intra-arterially in conscious animals. The increase in plasma renin activity was also unchanged by both rofecoxib and NS-398. The number of glomeruli with a renin-positive juxtaglomerular apparatus was elevated in clipped kidneys and decreased in contralateral kidneys of 2K1C rats. This pattern was unaltered by COX-2 inhibition. To test the effects of COX-2 blockade on a primarily macula densa-mediated stimulus, we studied salt depletion for comparison. A low-salt diet induced a significant increase in plasma renin activity, which was partially inhibited by treatment with NS-398. We conclude that inhibition of COX-2 in established renovascular hypertension does not affect renin synthesis or release. Thus either COX-2 is not necessary for the macula densa mechanism or the macula densa is not important for maintaining high renin in renovascular hypertension.

Resetting of tubuloglomerular feedback: evidence for a humoral factor in tubular fluid

1984 ◽  
Vol 246 (4) ◽  
pp. F495-F500 ◽  
Author(s):  
D. A. Haberle ◽  
J. M. Davis
Keyword(s):  
Flow Rate ◽  
Juxtaglomerular Apparatus ◽  
Ringer Solution ◽  
Humoral Factor ◽  
Inhibitory Factor ◽  
Tubuloglomerular Feedback ◽  
Fluid Composition ◽  
Similar Magnitude ◽  
Feedback Responses

Experiments were performed on chronically salt-loaded rats to determine whether resetting of tubuloglomerular feedback is caused by changes in the sensitivity of the juxtaglomerular apparatus itself or by changes of tubular fluid composition. The feedback response was quantified in both salt-loaded and salt-deplete rats by measuring early proximal flow rate (EPF) during loop perfusion at 40, 10, and 0 nl/min using tubular fluid harvested from both groups and with Ringer solution. In salt-loaded rats endogenous tubular fluid produced only a small feedback response (EPF40-0 = 1.9 +/- 1.5 nl/min), whereas exogenous tubular fluid from salt-deplete rats or Ringer solution produced normal feedback responses (EPF40-0 = 15.4 +/- 2.0 and 10.6 +/- 1.7 nl/min, respectively). In salt-deplete rats, endogenous tubular fluid and Ringer solution produced feedback responses of similar magnitude (EPF40-0 = 14.2 +/- 1.8 and 13.0 +/- 2.0 nl/min, respectively) but exogenous tubular fluid from salt-loaded rats elicited only a small feedback response (EPF40-0 = 1.5 +/- 1.6 nl/min), indistinguishable from that seen in salt-loaded rats with endogenous tubular fluid. It is concluded that an inhibitory factor in the tubular fluid of chronically salt-loaded rats causes a reduction in tubuloglomerular feedback response.

Glucose-6-phosphate dehydrogenase and renin in kidneys of hypertensive or adrenalectomized rats

1959 ◽  
Vol 197 (4) ◽  
pp. 869-872 ◽  
Author(s):  
R. Hess ◽  
F. Gross
Keyword(s):  
Enzymatic Activity ◽  
Rat Kidney ◽  
Juxtaglomerular Apparatus ◽  
Macula Densa ◽  
Sodium Balance ◽  
Normal Rat ◽  
Distal Tubules ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Renin Content ◽  
Intact Rats

Using a histochemical method, moderately strong glucose-6-phosphate dehydrogenase activity can be demonstrated in the macula densa of the distal tubules in the normal rat kidney. In rats rendered hypertensive by overdosage with cortexone (DOC) and saline, this enzymatic activity was found to decrease almost to zero within 4 weeks. This change was more marked in unilaterally nephrectomized animals than in intact rats. Measured by bioassay, the renin content of kidney extracts from the same animals was found to decrease simultaneously with the loss of enzymatic activity in the macula cells. The reverse effect, a marked increase in activity of the macula densa, was obtained in adrenalectomized animals. It is suggested that both the macula densa cells and the juxtaglomerular apparatus are parts of a system which respond similarly to changes in sodium balance and which may be related to the formation of renin.

Autoradiographic demonstration of oxytocin-binding sites in the macula densa

1989 ◽  
Vol 257 (2) ◽  
pp. F310-F314 ◽  
Author(s):  
M. E. Stoeckel ◽  
M. J. Freund-Mercier
Keyword(s):  
Binding Sites ◽  
Cellular Localization ◽  
Rat Kidney ◽  
Juxtaglomerular Apparatus ◽  
Macula Densa ◽  
Tubuloglomerular Feedback ◽  
Binding Characteristics ◽  
Conventional Film ◽  
High Concentrations ◽  
Autoradiographic Technique

Specific oxytocin (OT)-binding sites were localized in the rat kidney with use of a selective 125I-labeled OT antagonist (125I-OTA). High concentrations of OT binding sites were detected on the juxtaglomerular apparatus with use of the conventional film autoradiographic technique. No labeling occurred on other renal structures. The cellular localization of the OT binding sites within the juxtaglomerular apparatus was studied in light microscope autoradiography, on semithin sections from paraformaldehyde-fixed kidney slices incubated in the presence of 125I-OTA. These preparations revealed selective labeling of the macula densa, mainly concentrated at the basal pole of the cells. Control experiments showed first that 125I-OTA binding characteristics were not noticeably altered by prior paraformaldehyde fixation of the kidneys and second that autoradiographic detection of the binding sites was not impaired by histological treatments following binding procedures. In view of the role of the macula densa in the tubuloglomerular feedback, the putative OT receptors of this structure might mediate the stimulatory effect of OT on glomerular filtration.

scholarly journals Direct demonstration of tubular fluid flow sensing by macula densa cells

2010 ◽  
Vol 299 (5) ◽  
pp. F1087-F1093 ◽  
Author(s):  
Arnold Sipos ◽  
Sarah Vargas ◽  
János Peti-Peterdi
Keyword(s):  
Smooth Muscle ◽  
Fluid Flow ◽  
Smooth Muscle Cells ◽  
Flow Rate ◽  
Muscle Cells ◽  
Macula Densa ◽  
Fluid Composition ◽  
Apical Surface ◽  
Fluid Flow Rate ◽  
Flow Sensing

Macula densa (MD) cells in the cortical thick ascending limb (cTAL) detect variations in tubular fluid composition and transmit signals to the afferent arteriole (AA) that control glomerular filtration rate [tubuloglomerular feedback (TGF)]. Increases in tubular salt at the MD that normally parallel elevations in tubular fluid flow rate are well accepted as the trigger of TGF. The present study aimed to test whether MD cells can detect variations in tubular fluid flow rate per se. Calcium imaging of the in vitro microperfused isolated JGA-glomerulus complex dissected from mice was performed using fluo-4 and fluorescence microscopy. Increasing cTAL flow from 2 to 20 nl/min (80 mM [NaCl]) rapidly produced significant elevations in cytosolic Ca2+ concentration ([Ca2+]i) in AA smooth muscle cells [evidenced by changes in fluo-4 intensity (F); F/F0 = 1.45 ± 0.11] and AA vasoconstriction. Complete removal of the cTAL around the MD plaque and application of laminar flow through a perfusion pipette directly to the MD apical surface essentially produced the same results even when low (10 mM) or zero NaCl solutions were used. Acetylated α-tubulin immunohistochemistry identified the presence of primary cilia in mouse MD cells. Under no flow conditions, bending MD cilia directly with a micropipette rapidly caused significant [Ca2+]i elevations in AA smooth muscle cells (fluo-4 F/F0: 1.60 ± 0.12) and vasoconstriction. P2 receptor blockade with suramin significantly reduced the flow-induced TGF, whereas scavenging superoxide with tempol did not. In conclusion, MD cells are equipped with a tubular flow-sensing mechanism that may contribute to MD cell function and TGF.

Anatomy of the juxtaglomerular apparatus

1979 ◽  
Vol 237 (5) ◽  
pp. F333-F343 ◽  
Author(s):  
L. Barajas
Keyword(s):  
Secretory Granules ◽  
Distal Tubule ◽  
Juxtaglomerular Apparatus ◽  
Nerve Fibers ◽  
Basement Membranes ◽  
Macula Densa ◽  
Simple Type ◽  
Vascular Component ◽  
Tubular Components ◽  
Tubular Component

The juxtaglomerular apparatus, located in the glomerular hilum, consists of a vascular component (afferent and efferent arterioles and extraglomerular mesangium) and a tubular component (macula densa). Two types of contact between vascular and tubular components are observed: a) a complex type, involving distal tubule, extraglomerular mesangium, and proximal efferent arteriole, and b) a simple type, consisting of apposition of the basement membranes of the vascular and tubular components. Juxtaglomerular granular cells, the source of renin, are present throughout the vascular component but are more numerous in the afferent arteriole. They can be considered as "myoendocrine" cells, since they contain myofibrils and attachment bodies, together with secretory granules and crystalline protogranules. Macula densa cells differ from those elsewhere in the distal tubule in that their nuclei are closer to each other, the Golgi apparatus is basally located, and their basal membrane infoldings are less prominent. Adrenergic nerves are demonstrable by fluorescence histochemistry in the juxtaglomerular region. Electron microscopy reveals unmyelinated nerve fibers containing small dense-cored vesicles and capable, as shown by ultrastructural autoradiography, of incorporating exogenous tritiated norepinephrine. Neuroeffector junctions occur between nerves and cells of the vascular and, less frequently, the tubular component. In addition, adrenergic axons are observed in a juxtaglomerular cell tumor. Nerve terminals are seen in direct contact with the tumor cells.

scholarly journals Tubuloglomerular feedback and renin secretion in NTPDase1/CD39-deficient mice

2008 ◽  
Vol 294 (4) ◽  
pp. F965-F970 ◽  
Author(s):  
Mona Oppermann ◽  
David J. Friedman ◽  
Robert Faulhaber-Walter ◽  
Diane Mizel ◽  
Hayo Castrop ◽  
...  
Keyword(s):  
Signal Transmission ◽  
Critical Role ◽  
Juxtaglomerular Apparatus ◽  
Macula Densa ◽  
Renin Secretion ◽  
Tubuloglomerular Feedback ◽  
Salt Loading ◽  
Dependent Inhibition ◽  
Proximal Tubular ◽  
Deficient Mice

Studies in mice with null mutations of adenosine 1 receptor or ecto-5′-nucleotidase genes suggest a critical role of adenosine and its precursor 5′-AMP in tubulovascular signaling. To assess whether the source of juxtaglomerular nucleotides can be traced back to ATP dephosphorylation, experiments were performed in mice with a deficiency in NTPDase1/CD39, an ecto-ATPase catalyzing the formation of AMP from ATP and ADP. Urine osmolarity and glomerular filtration rate (GFR) were indistinguishable between NTPDase1/CD39−/− and wild-type (WT) mice. Maximum tubuloglomerular feedback (TGF) responses, as determined by proximal tubular stop flow pressure measurements, were reduced in NTPDase1/CD39−/− mice compared with controls (4.2 ± 0.9 vs. 10.5 ± 1.2 mmHg, respectively; P = 0.0002). Residual TGF responses gradually diminished after repeated changes in tubular perfusion flow averaging 2.9 ± 0.9 (on response) and 3.5 ± 1.1 (off response) mmHg after the second and 2.2 ± 0.5 (on response) and 1.5 ± 0.8 (off response) mmHg after the third challenge, whereas no fading of TGF responsiveness was observed in WT mice. Macula densa-dependent and pressure-dependent inhibition of renin secretion, as assessed by acute salt loading and phenylephrine injection, respectively, were intact in NTPDase1/CD39-deficient mice. In summary, NTPDase1/CD39-deficient mice showed a markedly compromised TGF regulation of GFR. These data support the concept of an extracellular dephosphorylation cascade during tubular-vascular signal transmission in the juxtaglomerular apparatus that is initiated by a regulated release of ATP from macula densa cells and results in adenosine-mediated afferent arteriole constriction.

Active and Inactive Renin in Individual Juxtaglomerular Apparatuses

1980 ◽  
Vol 59 (s6) ◽  
pp. 35s-36s
Author(s):  
A. Gillies ◽  
T. Morgan ◽  
W. Fitzgibbon
Keyword(s):  
Salt Intake ◽  
Active Form ◽  
Juxtaglomerular Apparatus ◽  
Macula Densa ◽  
Active Renin ◽  
High Salt Intake ◽  
Before And After ◽  
Inactive Renin ◽  
Inhibitor Of Protein Synthesis

1. Renin was measured in individual juxtaglomerular apparatuses before and after acidification in vitro.. 2. Active renin increased with delivery of extra sodium by microperfusion to the macula densa and this increase was similar to that achieved with acidification. 3. In rats pretreated with an inhibitor of protein synthesis active renin increased when extra sodium was delivered to the macula densa. 4. Salt intake changed the amount of renin present in the juxtaglomerular apparatus. In rats on a high salt intake the total renin was low and was all in an active form.

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