Faculty Opinions recommendation of Maintained tubuloglomerular feedback responses during acute inhibition of P2 purinergic receptors in mice.

2011 ◽  
Author(s):  
John Lorenz
Keyword(s):  
Purinergic Receptors ◽  
Tubuloglomerular Feedback ◽  
P2 Purinergic Receptors ◽  
Feedback Responses

scholarly journals Maintained tubuloglomerular feedback responses during acute inhibition of P2 purinergic receptors in mice

2011 ◽  
Vol 300 (2) ◽  
pp. F339-F344 ◽  
Author(s):  
Jurgen Schnermann
Keyword(s):  
Blood Pressure ◽  
Purinergic Receptors ◽  
Blood Pressure Response ◽  
Tubuloglomerular Feedback ◽  
Arterial Blood ◽  
P2 Purinergic Receptors ◽  
Arteriolar Resistance ◽  
Proximal Tubular ◽  
Different Strains

Tubuloglomerular feedback (TGF), the change of afferent arteriolar resistance initiated by changes of luminal NaCl concentration, is thought to be related to NaCl-dependent release of ATP by macula densa cells. In the present study, we have explored the possibility that the released ATP may directly interact with vasoconstrictor P2 purinergic receptors in the vicinity of the glomerular vascular pole. In two different strains of wild-type mice (SWR/J and FVB), TGF responses were determined in vivo by measuring the stop flow pressure (PSF) change caused by a saturating increase in loop of Henle flow rate before and during the administration of the P2 receptor inhibitors PPADS (12 mg/kg + 35 mg·kg−1·h−1 iv) or suramin (50 mg/kg + 150 mg·kg−1·h−1). Both agents significantly reduced the blood pressure response to the P2X agonist α,β-methylene ATP. In SWR/J and FVB mice, elevating flow to 30 nl/min reduced PSF by 16.4 ± 2.2 and 17.1 ± 1.8%. During infusion of PPADS, PSF fell by 18.8 ± 2 ( P = 0.4) and 16.5 ± 1.5% ( P = 0.82) in the two strains of mice. During suramin infusion, PSF decreased by 14.7 ± 2.4 ( P = 0.62) and 15 ± 1.3% ( P = 0.4) in SWR/J and FVB mice, respectively. Including PPADS (10−4 M) in the loop perfusate did not significantly alter the PSF response (18.9 ± 1.8%; P = 0.54). Arterial blood pressure was not systematically affected by the P2 inhibitors. As measured by free-flow micropuncture, PPADS significantly reduced proximal tubular fluid reabsorption in both fractional and absolute terms. These results indicate that the direct activation of P2 purinergic receptors by ATP is not a major cause of TGF-induced vasoconstriction in vivo.

Dissociation of tubuloglomerular feedback responses from distal tubular chloride concentration in the rat

1981 ◽  
Vol 240 (2) ◽  
pp. F111-F119 ◽  
Author(s):  
P. D. Bell ◽  
C. B. McLean ◽  
L. G. Navar
Keyword(s):  
Chloride Concentration ◽  
Tubuloglomerular Feedback ◽  
Fluid Solution ◽  
Perfusion Rate ◽  
Receptor System ◽  
Retrograde Perfusion ◽  
Perfusion Studies ◽  
Flow Pressure ◽  
Stop Flow ◽  
Feedback Responses

Previous studies have demonstrated that stop-flow pressure (SFP) feedback responses can occur during orthograde perfusion with solutions having low amounts of sodium or chloride. However, retrograde perfusion studies have suggested a specific role for chloride concentration in mediating feedback responses. These studies were conducted to compare SFP feedback responses during orthograde and retrograde perfusion with an artificial tubular fluid solution (ATF) (Cl- = 135 meq/liter) and a Na+ isethionate solution (Cl- = 6 meq/liter). With ATF, increases in perfusion rate from 10 to 35 nl/min led to decreases in SFP of 11 +/- 1.4 mmHg, increases in distal tubular fluid Cl- of 46 +/- 4.9 meq/liter, and osmolality of 58 +/- 10 mosmol/kg. There were significant inverse relationships between SFP and changes in Cl- and osmolality. With Na+ isethionate, SFP decreased by 8.4 +/- 1.0 mmHg, osmolality increased by 43 +/- 8 mosmol/kg, and Cl- did not change. There was a significant relationship between SFP and osmolality, but not with Cl-. During retrograde perfusion at 15 nl/min, SFP decreased by 12 +/- 1.2 mmHg with ATF and by 12 +/- 1.2 mmHg with Na+ isethionate. These results demonstrate that feedback-mediated decreases in SFP can occur in the absence of concomitant increases in distal Cl- and suggest that the receptor system does not have a unique and specific requirement for chloride.

Opposing effects of captopril and aprotinin on tubuloglomerular feedback responses

1984 ◽  
Vol 247 (6) ◽  
pp. F912-F918 ◽  
Author(s):  
J. Schnermann ◽  
J. P. Briggs ◽  
G. Schubert ◽  
M. Marin-Grez
Keyword(s):  
Filtration Rate ◽  
Tubuloglomerular Feedback ◽  
Perfusion Rate ◽  
Kinin System ◽  
Single Nephron ◽  
Main Action ◽  
Kallikrein Kinin System ◽  
Opposing Effects ◽  
Different Doses ◽  
Feedback Responses

We investigated the effect of two protease inhibitors, captopril and aprotinin, on tubuloglomerular feedback. In anesthetized rats, 15 or 25 mg/kg captopril significantly reduced the change of early proximal flow rate achieved by raising loop of Henle perfusion rate from 0 to 40 nl/min. Consistent with this reduction of maximum responses, there was a rise of single nephron glomerular filtration rate from 30.7 +/- 1.15 to 35.0 +/- 0.93 nl/min (P less than 0.01) following 25 mg/kg captopril. Infusion of aprotinin at 40,000 KIU/h produced an increase in maximum feedback responses from 38.2 +/- 1.66 to 56.8 +/- 2.35% (P less than 0.05). Infusion of aprotinin in two different doses (20,000 or 40,000 KIU/h) diminished or prevented the effect of 25 mg/kg captopril on maximum feedback responses. Since the main action of aprotinin is believed to be kallikrein inhibition, our data suggest that the magnitude of feedback responses may be affected by the kallikrein-kinin system and that the action of captopril may be in part mediated by its interference with kinin metabolism.

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.

Failure of tubule fluid osmolarity to affect feedback regulation of glomerular filtration

1980 ◽  
Vol 239 (5) ◽  
pp. F427-F432 ◽  
Author(s):  
J. P. Briggs ◽  
J. Schnermann ◽  
F. S. Wright
Keyword(s):  
Flow Rate ◽  
Feedback Regulation ◽  
Solute Concentration ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Perfusion Flow ◽  
Sprague Dawley Rats ◽  
Nacl Concentration ◽  
Osmotic Agents ◽  
Feedback Responses

Experiments were performed in Sprague-Dawley rats in order to distinguish between sodium chloride and total solute concentration as possible luminal signals capable of eliciting tubuloglomerular feedback responses. Early proximal flow rate (VEP), an index of nephron filtration rate, was measured without perfusion of the loop of Henle and during retrograde perfusion with solutions containing 20, 35, 60 to 100 mM NaCl and varying amounts of either urea or mannitol to achieve total solute concentrations of 130, 280, or 400 mosM. Perfusion flow rate was kept constant at 20 nl/min. Perfusion with a solution containing 20 mM NaCl and made hypo-, iso-, or hypertonic with urea or mannitol caused little or no change in VEP. Perfusion with a 35 mM NaCl solution made hypo-, iso-, or hypertonic with mannitol resulted in a fall of VEP of 6-7 nl/min. When NaCl concentration was 60 mM, VEP fell by 10-14 nl/min with solutions made hypo-, iso-, or hypertonic with urea or mannitol. With 100 mM NaCl solutions made hypo-, iso-, or hypertonic with mannitol, VEP fell approximately 12 nl/min. These results indicate that feedback responses are determined by the NaCl concentration of the perfusate and that this NaCl dependency is not modified by varying perfusate osmolarity between 130 and 400 mosM with urea or mannitol as osmotic agents.

scholarly journals Purinergic signaling, DAMPs, and inflammation

2020 ◽  
Vol 318 (5) ◽  
pp. C832-C835 ◽  
Author(s):  
Francesco Di Virgilio ◽  
Alba Clara Sarti ◽  
Robson Coutinho-Silva
Keyword(s):  
Plasma Membrane ◽  
Purinergic Receptors ◽  
Purinergic Signaling ◽  
Extracellular Atp ◽  
Main Metabolite ◽  
P2 Purinergic Receptors ◽  
Evolutionary Features ◽  
Multicellular Organisms ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Danger sensing is one of the most fundamental evolutionary features enabling multicellular organisms to perceive potential threats, escape from risky situations, fight actual intruders, and repair damage. Several endogenous molecules are used to “signal damage,” currently referred to as “alarmins” or “damage-associated molecular patterns” (DAMPs), most being already present within all cells (preformed DAMPs), and thus ready to be released, and others neosynthesized following injury. Over recent years it has become overwhelmingly clear that adenosine 5′-triphosphate (ATP) is a ubiquitous and extremely efficient DAMP (thus promoting inflammation), and its main metabolite, adenosine, is a strong immunosuppressant (thus dampening inflammation). Extracellular ATP ligates and activates the P2 purinergic receptors (P2Rs) and is then degraded by soluble and plasma membrane ecto-nucleotidases to generate adenosine acting at P1 purinergic receptors (P1Rs). Extracellular ATP, P2Rs, ecto-nucleotidases, adenosine, and P1Rs are basic elements of the purinergic signaling network and fundamental pillars of inflammation.

Enhanced tubuloglomerular feedback during peritubular infusions of angiotensins I and II

1988 ◽  
Vol 255 (3) ◽  
pp. F383-F390 ◽  
Author(s):  
K. D. Mitchell ◽  
L. G. Navar
Keyword(s):  
De Novo ◽  
Feedback Mechanism ◽  
Tubuloglomerular Feedback ◽  
Ang Ii ◽  
Angiotensin I ◽  
Peritubular Capillary ◽  
Perfusion Rate ◽  
Flow Pressure ◽  
Stop Flow ◽  
Feedback Responses

Experiments were performed in pentobarbital sodium-anesthetized rats to determine whether increases in intrarenal generation of angiotensin II (ANG II) can enhance the sensitivity of the tubuloglomerular feedback mechanism. Stop-flow pressure (SFP) feedback responses to step increases in late proximal perfusion rate were obtained during control conditions and during simultaneous peritubular capillary infusion of either angiotensin I (ANG I) or ANG II. Infusion of either 10(-7) M ANG II or 10(-5) M ANG I, at rates (18.3 +/- 0.9 and 14.8 +/- 1.5 nl/min, respectively) that did not affect resting SFP, enhanced the magnitude of SFP feedback responses both at a low proximal perfusion rate of 10 nl/min (2.9 +/- 0.9 vs. 0.3 +/- 0.2 and 4.5 +/- 1.0 vs. 0.1 +/- 0.1 mmHg, respectively) and at proximal perfusion rates (greater than 30 nl/min) that elicited a maximal feedback response (13.1 +/- 1.0 vs. 10.1 +/- 0.7 and 13.5 +/- 1.6 vs. 9.8 +/- 0.8 mmHg, respectively). With a higher ANG I infusion rate (20 nl/min), control SFP measured in the absence of distal volume delivery decreased from 39.2 +/- 0.6 to 12.0 +/- 2.8 mmHg (n = 18). These effects were blocked when the ANG II receptor antagonist, saralasin (10(-5) M, Sar), was added to the infusate. In addition, the magnitude of the maximal SFP feedback response was not altered during infusion of Sar alone or ANG I + Sar. These findings indicate that ANG II, either added or formed de novo beyond the glomerular circulation, can enhance the sensitivity of the tubuloglomerular feedback mechanism.

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