scholarly journals Adenosine A2 receptors modulate tubuloglomerular feedback

2010 ◽  
Vol 299 (2) ◽  
pp. F412-F417 ◽  
Author(s):  
Mattias Carlström ◽  
Christopher S. Wilcox ◽  
William J. Welch
Keyword(s):  
Receptor Antagonist ◽  
Low Dose ◽  
Tubuloglomerular Feedback ◽  
High Dose ◽  
Sprague Dawley ◽  
Simultaneous Application ◽  
Sprague Dawley Rats ◽  
Flow Pressure ◽  
Stop Flow ◽  
A2 Receptors

Adenosine can mediate the tubuloglomerular (TGF) response via activation of A1 receptors on the afferent arteriole, but both adenosine A1 and A2 receptors can regulate preglomerular resistance. We tested the hypothesis that adenosine A2 receptors offset the effect of A1 receptors and modulate the TGF. Maximal TGF responses were measured in male Sprague-Dawley rats as changes in proximal stop-flow pressure (ΔPSF) in response to increased perfusion of the loop of Henle (0 to 40 nl/min) with artificial tubular fluid (ATF). The maximal TGF response was studied after 5 min of intratubular perfusion (10 nl/min) with ATF alone, or with ATF plus the A2A receptor antagonist (ZM-241385; 10−7 or 10−5 mol/l), A1 receptor antagonist (PSB-36; 10−8 mol/l), or with a combination of A1 (PSB-36; 10−8 mol/l) and A2A (ZM-241385; 10−7 mol/l) antagonists. The maximal TGF response (ΔPSF) with ATF alone was 11.7 ± 1.0 mmHg. Specific A2 inhibition (low dose) enhanced the maximal TGF response (15.7 ± 0.8 mmHg; P < 0.01), whereas a high dose (unspecific inhibition) attenuated the response (5.0 ± 0.4 mmHg; P < 0.001). A1 inhibition alone led to a paradoxical TGF response, with an increase in PSF of 3.1 ± 0.5 mmHg ( P < 0.05). Simultaneous application of A1 and A2 antagonists abolished the TGF response (ΔPSF: 0.4 ± 0.3 mmHg). In conclusion, adenosine A2 receptors modulate the TGF response by counteracting the effects of adenosine A1 receptors.

scholarly journals Testosterone enhances tubuloglomerular feedback by increasing superoxide production in the macula densa

2013 ◽  
Vol 304 (9) ◽  
pp. R726-R733 ◽  
Author(s):  
Yiling Fu ◽  
Yan Lu ◽  
Eddie Y. Liu ◽  
Xiaolong Zhu ◽  
Gouri J. Mahajan ◽  
...  
Keyword(s):  
Macula Densa ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Mediated Effects ◽  
Sprague Dawley Rats ◽  
Flow Pressure ◽  
Laser Capture ◽  
Stop Flow ◽  
Dependent Pathway

Males have higher prevalence of hypertension and renal injury than females, which may be attributed in part to androgen-mediated effects on renal hemodynamics. Tubuloglomerular feedback (TGF) is an important mechanism in control of renal microcirculation. The present study examines the role of testosterone in the regulation of TGF responses. TGF was measured by micropuncture (change of stop-flow pressure, ΔPsf) in castrated Sprague-Dawley rats. The addition of testosterone (10−7 mol/l) into the lumen increased the ΔPsf from 10.1 ± 1.2 to 12.2 ± 1.2 mmHg. To determine whether androgen receptors (AR) are involved, mRNA of AR was measured in the macula dense cells isolated by laser capture microdissection from kidneys, and a macula densa-like cell line (MMDD1). AR mRNA was expressed in the macula densa of rats and in MMDD1 cells. We next examined the effects of the AR blocker, flutamide (10−5 mol/l) on the TGF response. The addition of flutamide blocked the effects of testosterone on TGF. The addition of Tempol (10−4 mol/l) or polyethylene glycol-superoxide dismutase (100 U/ml) to scavenge superoxide blocked the effect of testosterone to augment TGF. We then applied apocynin to inhibit NAD(P)H oxidase and oxypurinol to inhibit xanthine oxidase and found the testosterone-induced augmentation of TGF was blocked. In additional experiments in MMDD1 cells, we found that testosterone increased O2− generation. Apocynin or oxypurinol blocked the testosterone-induced increases of O2−, while blockade of COX-2 with NS-398 had no effect. These findings suggest that testosterone enhances TGF response by stimulating O2− production in macula densa via an AR-dependent pathway.

Tubuloglomerular feedback and tubular reabsorption during acute potassium loading in rats

1994 ◽  
Vol 267 (2) ◽  
pp. F223-F230 ◽  
Author(s):  
B. Braam ◽  
P. Boer ◽  
H. A. Koomans
Keyword(s):  
Distal Tubule ◽  
Plasma Potassium ◽  
Tubuloglomerular Feedback ◽  
Control Group ◽  
Sprague Dawley ◽  
Time Control ◽  
Sprague Dawley Rats ◽  
Single Nephron ◽  
Flow Pressure ◽  
Potassium Loading

Acute hyperkalemia has been associated with changes in reabsorption, glomerular filtration rate (GFR), and autoregulation, which might represent altered tubuloglomerular feedback (TGF) responsiveness. Therefore, TGF responsiveness, segmental reabsorption of water, sodium and potassium, and single-nephron GFR were evaluated during acute potassium loading in male Sprague-Dawley rats. Rats receiving 300 mM KNO3, KHCO3, and KCl showed significantly increased plasma potassium levels and attenuation of stop-flow pressure responses 45-90 min after starting the potassium infusion compared with that observed in time controls and rats infused with 300 mM NaCl. Attenuation of TGF responsiveness could not be related to plasma and kidney angiotensin II levels. Segmental water and sodium handling and proximal to distal single-nephron GFR differences assessed in a time control group and a group receiving 300 mM KCl revealed no changes related to KCl infusion. However, late proximal and early distal potassium concentrations increased significantly from 4.7 +/- 0.2 to 6.3 +/- 0.3 mM (P < 0.01) and from 1.5 +/- 0.1 to 2.7 +/- 0.4 mM (P < 0.01), respectively. In summary, although attenuated TGF responsiveness was demonstrated at higher perfusion rates, this study does not support a significant role for either the TGF mechanism or changes in reabsorption upstream of the early distal tubule for the initiation of kaliuresis during acute potassium loading.

Inhibition of tubuloglomerular feedback during adenosine1 receptor blockade

1990 ◽  
Vol 258 (3) ◽  
pp. F553-F561 ◽  
Author(s):  
J. Schnermann ◽  
H. Weihprecht ◽  
J. P. Briggs
Keyword(s):  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Tubuloglomerular Feedback ◽  
Receptor Blockade ◽  
Peritubular Capillary ◽  
Maximum Change ◽  
A1 Receptor ◽  
Afferent Arterioles ◽  
Flow Pressure ◽  
Stop Flow

Experiments were performed in anesthetized rats to study the effect of the selective adenosine1 (A1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX) on tubuloglomerular feedback (TGF) responses assessed as the maximum change of stop-flow pressure (PSF). Compared with control, PSF responses were reduced during luminal application of CPX at 10(-4) and 10(-5)M (-4.9 +/- 0.44 vs. + 0.9 +/- 0.42 mmHg and -6.8 +/- 0.69 vs. -1.4 +/- 0.7 mmHg, respectively), during peritubular administration of CPX at 10(-4)M (-6.2 +/- 0.44 vs. -2.8 +/- 0.42 mmHg), and during infusion of CPX at 10(-4) M into the lumen of a neighboring nephron (-5.6 +/- 0.6 vs. -1.98 +/- 0.51 mmHg). Selectivity of CPX was tested by studying its effect on the PSF reduction produced by the A1-receptor agonist N6-cyclohexyladenosine (CHA). CHA at 10(-5)M reduced PSF when infused into the peritubular blood (-11.8 +/- 3.7 mmHg), and this effect was blunted by luminal application of CPX (-1.5 +/- 0.6 mmHg). CHA also reduced PSF when infused into a neighboring nephron, and this effect was blunted by infusing CPX at 10(-4)M into the same neighboring nephron, a different neighboring nephron, or a peritubular capillary. These results are consistent with the concept that activation of A1-receptors on vascular cells of the afferent arterioles participates in the mediation of TGF responses.

Sympathetic and parasympathetic component of bradycardia triggered by stimulation of NTS P2X receptors

2006 ◽  
Vol 290 (2) ◽  
pp. H807-H812 ◽  
Author(s):  
Amy M. Kitchen ◽  
Donal S. O'Leary ◽  
Tadeusz J. Scislo
Keyword(s):  
Low Dose ◽  
Nucleus Tractus Solitarius ◽  
Receptor Activation ◽  
P2x Receptors ◽  
P2x Receptor ◽  
High Dose ◽  
Adrenergic Blockade ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Stimulation Of

We have previously shown that activation of P2X purinoceptors in the subpostremal nucleus tractus solitarius (NTS) produces a rapid bradycardia and hypotension. This bradycardia could occur via sympathetic withdrawal, parasympathetic activation, or a combination of both mechanisms. Thus we investigated the relative roles of parasympathetic activation and sympathetic withdrawal in mediating this bradycardia in chloralose-urethane anesthetized male Sprague-Dawley rats. Microinjections of the selective P2X purinoceptor agonist α,β-methylene ATP (25 pmol/50 nl and 100 pmol/50 nl) were made into the subpostremal NTS in control animals, after atenolol (2 mg/kg iv), a β1-selective antagonist, and after atropine methyl bromide (2 mg/kg iv), a muscarinic receptor antagonist. The bradycardia observed with activation of P2X receptors at the low dose of the agonist is mediated almost entirely by sympathetic withdrawal. After β1-adrenergic blockade, the bradycardia was reduced to just −5.1 ± 0.5 versus −28.8 ± 5.1 beats/min in intact animals. Muscarinic blockade did not produce any significant change in the bradycardic response at the low dose. At the high dose, both β1-adrenergic blockade and muscarinic blockade attenuated the bradycardia similarly, −37.4 ± 6.4 and −40.6 ± 3.7 beats/min, respectively, compared with −88.0 ± 11 beats/min in control animals. Double blockade of both β1-adrenergic and muscarinic receptors virtually abolished the response (−2.5 ± 0.8 beats/min). We conclude that the relative contributions of parasympathetic activation and sympathetic withdrawal are dependent on the extent of P2X receptor activation.

scholarly journals Nitric oxide release as an essential mitigating step in tubuloglomerular feedback: observations during intrarenal nitric oxide clamp.

1998 ◽  
Vol 9 (9) ◽  
pp. 1596-1603
Author(s):  
E Turkstra ◽  
B Braam ◽  
H A Koomans
Keyword(s):  
Nitric Oxide ◽  
Macula Densa ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Arginine Infusion ◽  
Nitric Oxide Release ◽  
Sprague Dawley Rats ◽  
Flow Pressure ◽  
Oxide Synthase ◽  
Nitroprusside Infusion

Nitric oxide synthase inhibition in the kidney enhances tubuloglomerular feedback (TGF) responsiveness. This may reflect either the effect of reduced basal nitric oxide (NO) availability or the effect of impaired NO release that is physiologically induced by TGF activation. However, it is unknown whether the latter actually takes place. In this study, it was hypothesized that NO is released (from macula densa cells or endothelium) as part of the normal TGF loop, and mitigates the TGF response. In Sprague Dawley rats, TGF responsiveness was assessed (fall in tubular stop flow pressure, deltaSFP, upon switching loop of Henle perfusion rates from 0 to 40 nl/min) during an intrarenal NO clamp (systemic infusion of nitro-L-arginine, 10 microg/kg per min, followed by intrarenal nitroprusside infusion adjusted to restore renal blood flow [RBF]). This maneuver was presumed to fix intrarenal NO impact at a physiologic level. To validate the approach, TGF responsiveness during an intrarenal angiotensin II (AngII) clamp (systemic infusion of enalaprilat 0.2 mg/kg per min, followed by intrarenal AngII infusion) was also studied. AngII is presumed to modulate but not mediate, TGF, thus not to increase as part of the TGF loop. In untreated animals, RBF was 7.4 +/- 0.4 ml/min, and deltaSFP was 5.7 +/- 1.6 mmHg. Nitro-L-arginine infusion alone reduced RBF to 5.3 +/- 0.5 ml/min (P < 0.05); with nitroprusside infusion, RBF was restored to 8.3 +/- 0.7 ml/min. In this condition (NO clamp), deltaSFP was markedly increased to 19.6 +/- 3.2 mmHg (P < 0.05). By contrast, deltaSFP, which was virtually abolished during enalaprilat alone (0.2 +/- 0.3 mmHg), was not significantly different from controls during AngII clamp (8.2 +/- 1.0 mmHg). These data suggest that NO may well be released upon TGF activation. By contrast, AngII is not dynamically involved in TGF activation, but may modulate the TGF response. Thus, dynamic release of NO during TGF activation mitigates the TGF response, so that it will offset the action of a primary, as yet undefined, vasoconstrictor mediator. The source of this NO, macula densa or endothelium, remains to be elucidated.

The effect of tubular perfusion with PGE2, PGF2α, and PGI2 on the tubuloglomerular feedback control in the rat

1983 ◽  
Vol 61 (11) ◽  
pp. 1317-1323 ◽  
Author(s):  
A. Erik G. Persson ◽  
Bengt Hahne ◽  
Göran Selén
Keyword(s):  
Control Level ◽  
Renal Medulla ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Perfusion Solution ◽  
Sprague Dawley Rats ◽  
Feedback Sensitivity ◽  
Proximal Tubular ◽  
Flow Pressure ◽  
Tubular Flow

The prostaglandins (PG) of the renal medulla might affect the nephron and the cortical arteriolar function via the tubular route. To investigate this question PGE2 (1 μg/mL), PGF2α (10 μg/mL), or PGI2 (1 ng/mL) was added to the tubular perfusion solution when the characteristics of the tubuloglomerular feedback (TGF) control were measured. The experiments were performed on Sprague–Dawley rats. The proximal tubular stop-flow pressure (PSF) was measured upstream to a wax block, while at the same time the distal nephron was perfused with prostaglandin-containing or prostaglandin-free solutions at different flow rates varying from 0 to 50 nL/min. The maximal drop in PSF (ΔPSF) and the tubular flow rate at which 50% of the ΔPSF response was obtained, the turning point (TP), were determined. When PGE2 or PGF2α was added to the tubular perfusion solution in the control animals a significant increase in feedback sensitivity was found. After 10 min of tubular PGI2 perfusion the feedback sensitivity was almost completely abolished, with a ΔPSF of 0.8 mmHg (1 mmHg = 133.322 Pa) (control 8.4 mmHg) and a TP of >40 nL/min (control 22 nL/min). After nephrectomy the feedback sensitivity was reduced, with a ΔPSF of 2.0 mmHg and a TP of >40 nL/min. When PGE2 was added to the tubular perfusion solution in the uninephrectomized animals, the feedback sensitivity was increased to the control level, with a ΔPSF of 8.2 mmHg and a TP of 20.0 nL/min. The results show that PGI2 reduces and PGE2 and PGF2α increase TGF sensitivity when added to the tubular perfusion solution and that the decrease seen after nephrectomy is again reset to the control level by intratubular PGE2 administration.

scholarly journals Androgenic Effects of Cinnamomum camphora in Male Sprague-dawley Rats

2019 ◽  
pp. 1-13
Author(s):  
O. H. Ayoade ◽  
G. G. Akunna ◽  
F. I. Duru
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Activity Level ◽  
Control Group ◽  
High Dose ◽  
Activity Levels ◽  
Sprague Dawley ◽  
Treatment Groups ◽  
Sprague Dawley Rats ◽  
Medium Dose

This study evaluated camphora-induced androgenic and histopathological changes in male Sprague-Dawley rats. Thirty-five animals weighing 200 g±20 g were used for this study and randomly divided equally into five groups, with seven rats in each group. Group A animals (normal control group) were served water and rat chow only; Groups B-D (treatment groups) were orally administered camphora in doses of 1 g/kg (Low-dose), 2 g/kg (Medium-dose) and 4 g/kg (High-dose) respectively while Group E (vehicle group) were orally administered 6 mL/kg olive oil (a solvent for camphora) per day for 56 days. There was a significant decrease (P< .05) in activity levels of Follicle-Stimulating Hormone (FSH); Superoxide Dismutase (SOD) when the treatment was compared with the control group. Also, a significant decrease (P< .05) in activity level of FSH was observed when the Medium-dose group was compared with Low-dose group. Insignificant irregular pattern in activity level of Testosterone was observed across the treatment groups when compared with the control. However, a significant increase (P< .05) in activity level of Testosterone was observed when the High-dose group was compared with the Medium-dose group. There was a significant increase (P< .05) in activity levels of Luteinizing Hormone (LH) and Malondialdehyde (MDA) when the treatment was compared with the control group. Semen analysis showed reduction in sperm concentration, motility and morphology with increasing concentration of camphora. Significant decrease was recorded in testicular weight when High-dose group was compared to Control and Low-dose groups. Histopathological changes were seen in the testes of the camphor administered groups, ranging from mild disintegrated interstitial tissues in Low-dose to severe degeneration and disintegration of both seminiferous and interstitial tissues in the testes in the Medium-dose and High-dose groups. In conclusion, camphora had androgenic and toxic effects on testis and may cause testicular tissue damage.

Magnitude of TGF-initiated nephron-nephron interactions is increased in SHR

1995 ◽  
Vol 269 (2) ◽  
pp. F198-F204 ◽  
Author(s):  
Y. M. Chen ◽  
K. P. Yip ◽  
D. J. Marsh ◽  
N. H. Holstein-Rathlou
Keyword(s):  
Interaction Strength ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Vascular Connection ◽  
Spontaneously Hypertensive ◽  
Sd Rats ◽  
Flow Pressure ◽  
Stop Flow ◽  
Account Interaction

We compared the tubuloglomerular feedback (TGF)-initiated nephron-nephron interaction in spontaneously hypertensive rats (SHR) and normotensive Sprague-Dawley (SD) rats. Interaction strength was assessed by measuring stop-flow pressure (delta SFP) responses in pairs of nephrons, where only one nephron of the pair was microperfused. The vascular connection was determined from casts of the nephrons and vessels; length of arteriolar separation between the two glomeruli was measured on the casts. When microperfusion rate was increased from 5 to 50 nl/min, delta SFP in perfused nephrons was 10.6 +/- 0.6 and 10.2 +/- 0.7 mmHg [not significant (NS)] in SD and SHR, respectively. In the matched unperfused nephrons from the same cortical radial artery, delta SFP was 1.3 +/- 0.2 and 2.9 +/- 0.7 mmHg (P < 0.05) in SD and SHR. When the perfused and unperfused nephron originated from different cortical radial arteries, delta SFP in the unperfused nephrons was -0.1 +/- 0.2 and 0.0 +/- 0.3 mmHg (NS) in SD and SHR, respectively. In both strains, interaction strength varied inversely with glomerular separation. When the dependence on distance was taken into account, interaction strength was about threefold greater in SHR than in SD. We conclude that the nephron-nephron interaction is significantly greater in SHR. The dependence of interaction strength on distance separating the glomeruli suggests that the interaction is propagated along the preglomerular vasculature.

scholarly journals Effects of Chronic Exposure to Sodium Arsenite on Expressions of VEGF and VEGFR2 Proteins in the Epididymis of Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Dai Yan-Ping ◽  
Gao Xiao-Qin ◽  
Ma Xiao Ping ◽  
Yue Ying Quan
Keyword(s):  
Sodium Arsenite ◽  
Low Dose ◽  
Infected Group ◽  
Control Group ◽  
High Dose ◽  
Apoptotic Cells ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Group Protein

Objective. To study the expressions of VEGF and VEGFR2 at protein level in the epididymis of rats with arsenism. Methods. Forty male Sprague-Dawley rats were randomly divided into four groups: the high dose arsenic infected group (60.0 mg/L in water), the middle dose arsenic infected group (12.0 mg/L in water), the low dose arsenic infected group (2.4 mg/L in water), and the control group (distilled water). Rats were treated with arsenic through drinking water for 6 consecutive months. At the end of the experiment, the average densitometry values of apoptotic cells in epididymis tubules were determined by TUNEL method; the protein and mRNA levels of VEGF and VEGFR2 were observed by immunohistochemistry, Western blot, and real time fluorescent quantitative PCR, respectively. Results. Compared with the control group, in each infected group, the average densitometry values of apoptotic cells in the epididymis tubules were significantly lower. Compared with control group, protein and mRNA levels of VEGF and VEGFR2 in each infected group were obviously declined. The correlations between protein and mRNA levels of VEGF and VEGFR2 were positively exhibited (r = 0.843, 0.869, p < 0.05). Conclusions. Arsenism affects the expressions of VEGF and VEGFR2 in the epididymis of rats and results in apoptosis of pathophysiology of male infertility.

scholarly journals Effects of Tart Cherry Powder on Serum Uric Acid in Hyperuricemia Rat Model

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Ruirui Li ◽  
Yuefeng Tan ◽  
Yanxia Li ◽  
Xia Zhu ◽  
Xinyao Tang ◽  
...  
Keyword(s):  
Uric Acid ◽  
Serum Uric Acid ◽  
Low Dose ◽  
Kidney Injury ◽  
High Dose ◽  
Sprague Dawley ◽  
Tart Cherry ◽  
Sprague Dawley Rats ◽  
Adenosine Deaminase Activity ◽  
Anti Inflammation

Hyperuricemia, as a critical risk factor for various adverse clinical outcomes, shows a trend of increasing prevalence among young-aged population. Dietary adjuvant therapy by function foods, such as tart cherry, is promising. Thus, effects of tart cherry powder specialized in hyperuricemia were explored via establishing a hyperuricemia model in Sprague Dawley rats by cotreatment with oteracil potassium and adenine. The results indicated that low dose of tart cherry powder (0.17 g/kg·bw) showed effects on hyperuricemia by slightly decreasing serum uric acid and improving kidney injury, whereas high dose of tart cherry powder (0.50 g/kg·bw) could merely alleviate kidney injury. Meanwhile, adenosine deaminase activity rather than xanthine oxidase activity was affected at low dose, which reveals low dose of tarty cherry powder may be beneficial to hyperuricemia through reduction of ADA activity, and its reported potentials on antioxidation or anti-inflammation provide clues for further study.

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