Tubuloglomerular feedback activity in virgin and 12-day-pregnant rats

1985 ◽  
Vol 249 (1) ◽  
pp. F169-F173 ◽  
Author(s):  
C. Baylis ◽  
R. C. Blantz
Keyword(s):  
Plasma Volume ◽  
Filtration Rate ◽  
Distal Tubule ◽  
Feedback System ◽  
Proximal Tubules ◽  
Tubuloglomerular Feedback ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
The Difference ◽  
In Pregnancy

Tubuloglomerular feedback activity was evaluated by micropuncture and microperfusion techniques in virgin and 12-day-pregnant Munich-Wistar rats. Plasma volume increases in pregnancy, which could suppress feedback activity, thus contributing to the rise in glomerular filtration rate observed in normal midterm pregnancy. Late proximal tubules were microperfused at 0, 10, 20, and 40 nl/min and the resulting filtration rate in the same nephron was evaluated. Nephron filtration rate (SNGFR) in proximal and distal tubules of other nephrons was also measured to assess the degree of activation of the tubuloglomerular feedback system and the relation of the spontaneous (normal) late proximal flow rate and SNGFR (distal tubule collections). SNGFR decreased significantly (from the 0 nl/min perfusion value) when late proximal tubules were perfused at 20 and 40 nl/min in both virgin and 12-day-pregnant rats. Tubuloglomerular feedback activity was not suppressed in pregnancy, but the relationship between SNGFR and late proximal tubule perfusion rate was reset for a higher value for SNGFR. The difference between proximal and distal SNGFR suggests that the feedback system was more activated in the virgin than in the pregnant rat. Thus, in spite of the known increases in plasma volume that occur in pregnancy, the kidney does not sense this volume expansion as a stimulus to suppress feedback activity.

Chlorothiazide effect on feedback-mediated control of glomerular filtration rate

1989 ◽  
Vol 257 (1) ◽  
pp. F137-F144 ◽  
Author(s):  
M. D. Okusa ◽  
A. E. Persson ◽  
F. S. Wright
Keyword(s):  
Glomerular Filtration Rate ◽  
Proximal Tubule ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Distal Tubule ◽  
Feedback System ◽  
Sprague Dawley ◽  
Single Nephron ◽  
The Difference ◽  
Tubule Fluid

We examined the effect of chlorothiazide (CTZ) on the tubuloglomerular (TG) feedback system in anesthetized Sprague-Dawley rats. During infusion of CTZ (0.25 mg.kg body wt-1.min-1) we found that whole kidney glomerular filtration rate (GFR) decreased by 19% (1.0 +/- 0.1 vs. 0.8 +/- 0.1 ml/min; P less than 0.005). To asses the activity of the TG feedback system during CTZ administration we compared measurements of single-nephron (SN)GFR from tubule fluid sampled separately at proximal and distal sites. During CTZ administration, distally measured SNGFR decreased significantly by 16% (27.3 +/- 1.3 vs. 22.9 +/- 1.1 nl/min; P less than 0.025), whereas proximally measured SNGFR was unchanged. Thus the difference in SNGFR between proximal and distal determination increased during CTZ infusion (4.7 +/- 0.7 vs. 7.7 +/- 0.7 nl/min; P less than 0.025), indicating that CTZ suppresses GFR by TG feedback. Na, K, and Cl concentrations measured in the late proximal tubule fluid during control and CTZ infusions were similar. In early distal tubule fluid samples K and Cl concentrations were unaffected by CTZ infusion, whereas Na concentrations increased by 32% (47.9 +/- 2.7 vs. 63.1 +/- 2.4 mM; P less than 0.001). Proximal tubule microperfusion with 1.0 mM CTZ decreased transport rates of Na and water by approximately 40%, whereas the transport rate of Cl was not affected. In conclusion our results indicate that CTZ reduces GFR by activating TG feedback. The mechanism by which this occurs is in part due to an increase in the strength of the signal.

The effect of chronic hydrochlorothiazide administration on renal function in the rat

1986 ◽  
Vol 70 (4) ◽  
pp. 379-387 ◽  
Author(s):  
S. J. Walter ◽  
D. G. Shirley
Keyword(s):  
Filtration Rate ◽  
Distal Tubule ◽  
Inhibitory Effect ◽  
Proximal Convoluted Tubule ◽  
Proximal Tubules ◽  
Fluid Delivery ◽  
Collecting Ducts ◽  
Single Nephron ◽  
Distal Tubules ◽  
The Difference

1. Hydrochlorothiazide was administered at two doses to Long-Evans rats for 7–10 days. Both doses resulted in an initial natriuresis and diuresis. After 1 day of treatment the natriuresis abated, but the diuresis persisted. 2. The mechanisms responsible for these chronic effects were investigated by performing clearance and micropuncture studies on all animals; collections were made from late proximal tubules and from early and late regions of distal tubules. 3. Values for total glomerular filtration rate and single-nephron filtration rate in thiazide-treated rats were not significantly different from those in control animals. 4. The delivery of sodium to the end of the proximal convoluted tubule was considerably reduced in each group of thiazide-treated rats. Although sodium delivery to the early distal tubule was also significantly lower than in control animals, the difference had disappeared by the late distal tubule. 5. It is concluded that the return of sodium excretion to control levels during chronic hyrochlorothiazide administration is a consequence of increased fractional reabsorption by the proximal tubules, secondary to a thiazide-induced sodium depletion. This results in less sodium being delivered to the nephron site at which thiazides exert their major inhibitory effect. 6. Fluid delivery to the end of the proximal convoluted tubule and to the early distal tubule was significantly reduced in thiazide-treated rats; in animals given the higher dose of diuretic it was also significantly reduced at the end of the distal tubule. Nevertheless, in both thiazide-treated groups urine flow rate was elevated, suggesting that reabsorption of water from the collecting ducts is reduced during chronic thiazide administration.

Micropuncture analysis of single-nephron function in NHE3-deficient mice

1999 ◽  
Vol 277 (3) ◽  
pp. F447-F453 ◽  
Author(s):  
John N. Lorenz ◽  
Patrick J. Schultheis ◽  
Timothy Traynor ◽  
Gary E. Shull ◽  
Jürgen Schnermann
Keyword(s):  
Proximal Tubule ◽  
Filtration Rate ◽  
Distal Tubule ◽  
Transport Processes ◽  
Tubuloglomerular Feedback ◽  
Thick Ascending Limb ◽  
Fluid Reabsorption ◽  
Fluid Delivery ◽  
Single Nephron ◽  
Flow Pressure

The Na/H exchanger isoform 3 (NHE3) is expressed in the proximal tubule and thick ascending limb and contributes to the reabsorption of fluid and electrolytes in these segments. The contribution of NHE3 to fluid reabsorption was assessed by micropuncture in homozygous ( Nhe3 −/−) and heterozygous ( Nhe3 +/−) knockout mice, and in their wild-type (WT, Nhe3 +/+) littermates. Arterial pressure was lower in the Nhe3 −/−mice (89 ± 6 mmHg) compared with Nhe3 +/+ (118 ± 4) and Nhe3 +/−(108 ± 5). Collections from proximal and distal tubules demonstrated that proximal fluid reabsorption was blunted in both Nhe3 +/− and Nhe3 −/−mice (WT, 4.2 ± 0.3; Nhe3 +/−, 3.4 ± 0.2; and Nhe3 −/−, 2.6 ± 0.3 nl/min; P < 0.05). However, distal delivery of fluid was not different among the three groups of mice (WT, 3.3 ± 0.4 nl/min; Nhe3 +/−, 3.3 ± 0.2 nl/min; and Nhe3 −/−, 3.0 ± 0.4 nl/min; P < 0.05). In Nhe3 −/−mice, this compensation was largely attributable to decreased single-nephron glomerular filtration rate (SNGFR): 10.7 ± 0.9 nl/min in the Nhe3 +/+ vs. 6.6 ± 0.8 nl/min in the Nhe3 −/−, measured distally. Proximal-distal SNGFR differences in Nhe3 −/−mice indicated that much of the decrease in SNGFR was due to activation of tubuloglomerular feedback (TGF), and measurements of stop-flow pressure confirmed that TGF is intact in Nhe3 −/−animals. In contrast to Nhe3 −/−mice, normalization of early distal flow rate in Nhe3 +/−mice was not related to decreased SNGFR (9.9 ± 0.7 nl/min), but rather, to increased fluid reabsorption in the loop segment ( Nhe3 +/+, 2.6 ± 0.2; Nhe3 +/−, 3.6 ± 0.5 nl/min). We conclude that NHE3 is a major Na/H exchanger isoform mediating Na+ and fluid reabsorption in the proximal tubule. In animals with NHE3 deficiency, normalization of fluid delivery to the distal tubule is achieved through alterations in filtration rate and/or downstream transport processes.

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.

scholarly journals Increased renal α-epithelial sodium channel (ENAC) protein and increased ENAC activity in normal pregnancy

2010 ◽  
Vol 299 (5) ◽  
pp. R1326-R1332 ◽  
Author(s):  
Crystal West ◽  
Zheng Zhang ◽  
Geoffrey Ecker ◽  
Shyama M. E. Masilamani
Keyword(s):  
Plasma Volume ◽  
Late Pregnancy ◽  
Normal Pregnancy ◽  
In Vivo Studies ◽  
Volume Status ◽  
Plasma Volume Expansion ◽  
Pregnant Rats ◽  
Mineralocorticoid Receptor Antagonist ◽  
The Difference

Pregnancy-mediated sodium (Na) retention is required to provide an increase in plasma volume for the growing fetus. The mechanisms responsible for this Na retention are not clear. We first used a targeted proteomics approach and found that there were no changes in the protein abundance compared with virgin rats of the β or γ ENaC, type 3 Na+/H+ exchanger (NHE3), bumetanide-sensitive cotransporter (NKCC2), or NaCl cotransporter (NCC) in mid- or late pregnancy. In contrast, we observed marked increases in the abundance of the α-ENaC subunit. The plasma volume increased progressively during pregnancy with the greatest plasma volume being evident in late pregnancy. ENaC inhibition abolished the difference in plasma volume status between virgin and pregnant rats. To determine the in vivo activity of ENaC, we conducted in vivo studies of rats in late pregnancy ( days 18–20) and virgin rats to measure the natriuretic response to ENaC blockade (with benzamil). The in vivo activity of ENaC (UNaV postbenzamil-UNaV postvehicle) was markedly increased in late pregnancy, and this difference was abolished by pretreatment with the mineralocorticoid receptor antagonist, eplerenone. These findings demonstrate that the increased α-ENaC subunit of pregnancy is associated with an mineralocorticoid-dependent increase in ENaC activity. Further, we show that ENaC activity is a major contributor of plasma volume status in late pregnancy. These changes are likely to contribute to the renal sodium retention and plasma volume expansion required for an optimal pregnancy.

Effect of nitric oxide synthase inhibition on cardiovascular and hormonal regulation during pregnancy in the rat

2000 ◽  
Vol 78 (5) ◽  
pp. 423-427 ◽  
Author(s):  
Yunlong Zhang ◽  
Susan Kaufman
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Plasma Renin Activity ◽  
Plasma Volume ◽  
Atrial Natriuretic Factor ◽  
Plasma Renin ◽  
Renin Activity ◽  
Pregnant Rats ◽  
Oxide Synthase ◽  
In Pregnancy

Recent studies have shown that nitric oxide (NO) biosynthesis increases in pregnancy and that inhibition of nitric oxide synthase (NOS) induces some pathological processes characteristic of preeclampsia. The current project sought to study the effect of the NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 10 µg·min-1, sc for 7 days) on plasma volume, plasma atrial natriuretic factor (ANF), plasma endothelin-1 (ET), and plasma renin activity (PRA) during gestation in conscious rats. NOS inhibition caused mean arterial pressure to increase in both virgin and 21-day pregnant rats. Plasma volume fell in the pregnant rats [L-NAME, 4.5 ± 0.3 mL·100 g-1 body wt. (n = 7) vs. D-NAME, 6.8 ± 0.2 mL·100 g-1 body wt. (n = 10); P < 0.05] but not in the virgin rats [L-NAME, 4.3 ± 0.1 mL·100 g-1 body wt. (n = 6) vs. D-NAME, 4.8 ± 0.2 mL·100 g-1 body wt. (n = 8)]. There was no effect of NOS inhibition on plasma ANF levels or PRA in either the virgin or pregnant rats. However, L-NAME did decrease plasma ET levels in the pregnant rats [L-NAME, 19.6 ± 1.6 pg·mL-1 (n = 8) vs. D-NAME, 11.6 ± 2.5 pg·mL-1 (n = 9); P < 0.05]. Our results confirm that NO is involved in cardiovascular homeostasis in pregnancy; NOS inhibition selectively reduces plasma volume in pregnant rats, thus mimicking a major pathophysiological perturbation of preeclampsia. However, it does not induce the hormonal changes characteristic of preeclampsia, namely the decrease in PRA and increase in plasma ET and ANF levels. Key words: plasma volume, preeclampsia, endothelin, atrial natriuretic factor, plasma renin activity.

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.

Expression of rat hepatic multidrug resistance-associated proteins and organic anion transporters in pregnancy

2002 ◽  
Vol 283 (3) ◽  
pp. G757-G766 ◽  
Author(s):  
Jingsong Cao ◽  
Bruno Stieger ◽  
Peter J. Meier ◽  
Mary Vore
Keyword(s):  
Multidrug Resistance ◽  
Plasma Membranes ◽  
Organic Anion ◽  
Liver Homogenate ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Western Analysis ◽  
Anion Transporters ◽  
Intracellular Compartments ◽  
In Pregnancy

The expression of hepatic multidrug resistance-associated protein (Mrp)1, 2, 3, and 6 and organic anion transporting polypeptides (Oatp)1 and 2 were examined in control and 20- to 21-day pregnant rats. Western analysis showed that expression of Oatp2 was decreased 50% in pregnancy, whereas expression of Oatp1 did not change. Expression of Mrp2 protein determined by Western analysis of total liver homogenate decreased to 50% of control levels in pregnant rats, consistent with studies using plasma membranes. Confocal immunohistochemistry showed that Mrp2 expression was confined to the canalicular membrane in both control and pregnant rats and was not detectable in intracellular compartments. In isolated perfused liver, the biliary excretion of 2,4-dintrophenyl-glutathione was significantly decreased in pregnancy, consistent with decreased expression of Mrp2. The expression of the basolateral transporter Mrp1 was not altered in pregnancy, whereas expression of Mrp6 mRNA was decreased by 60%. Expression of Mrp3 was also decreased by 50% in pregnant rat liver, indicating differential regulation of Mrp isoforms in pregnancy. These data also demonstrate that decreased Mrp2 expression is not necessarily accompanied by increased Mrp3 expression.

scholarly journals Preclinical Trial of Traditional Plant Remedies for the Treatment of Complications of Gestational Malaria

Medicines ◽  
2021 ◽  
Vol 8 (12) ◽  
pp. 79
Author(s):  
Peter Uchenna Amadi ◽  
Emmanuel Nnabugwu Agomuo ◽  
Chinyere Nneka Ukaga ◽  
Uche Chinedu Njoku ◽  
Joy Adaku Amadi ◽  
...  
Keyword(s):  
Malaria In Pregnancy ◽  
Herbal Remedies ◽  
Therapeutic Effects ◽  
Pregnant Rats ◽  
Crown Rump Length ◽  
Preclinical Trial ◽  
Pregnant Rat ◽  
Average Percentage ◽  
Significant Difference ◽  
In Pregnancy

Background: Most pregnant women living in high malaria endemic regions of Nigeria use herbal remedies for the management of malaria-in-pregnancy, rather than the commonly prescribed drugs. Remedies common to this area involve a suspension of A. indica (AI) leaves and in some cases, a suspension containing a mixture of AI and D.edulis (PS). Aim: This study examined the therapeutic efficacies of AI, PS, or a combination of AI and PS in a pregnant rat model for exoerythrocytic stages of Plasmodium falciparum parasite. Method: A predetermined sample size of 30 dams was used (for a power level and confidence interval of 95%), and divided equally into six groups made up of non-malarous dams, untreated malarous dams, and malarous dams either treated exclusively with 1 mL of 3000 mg/kg b.w AI, 1000 mg/kg b.w PS, AI + PS (50% v/v), or 25 mg/kg b.w CQ. Result: No maternal mortality was recorded. AI significantly improved maternal weight gain from 32.4 to 82.2 g and placental weight from 0.44 to 0.53 g. In the curative test, AI and AI + PS significantly reduced the average percentage parasitemia (APP) in the pregnant rats from >80% to <20%. No significant difference in the APP was found between the pregnant rats treated with any of CQ or AI during the suppressive test. Results for the prophylactic test of the study groups showed that the APP was significantly reduced from 24.69% to 3.90% when treated with AI and 3.67% when combined with PS. AI + PS reduced diastolic blood pressure from 89.0 to 81.0 mm/Hg and compared with that of the non malarous dams. AI or AI + PS significantly increased the platelet counts (103 µL) from 214.1 to 364.5 and 351.2, respectively. AI and AI + PS improved birth weight from 2.5 to 3.9 g and crown rump length from 2.6 to 4.1 cm. For biomarkers of preeclampsia, combining AI and PS led to the reversal of the altered levels of creatine kinase, lactate dehydrogenase, cardiac troponin, soluble Fms-Like Tyrosine Kinase-1, and placental growth factor. Conclusions: This study validates the use of A. indica for the treatment of gestational malaria due to its antiplasmodial and related therapeutic effects and in combination with pear seeds for the management of malaria-in-pregnancy-induced preeclampsia.

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