scholarly journals Proximal tubule Na+/H+ exchanger activity in adult NHE8−/−, NHE3−/−, and NHE3−/−/NHE8−/− mice

2012 ◽  
Vol 303 (11) ◽  
pp. F1495-F1502 ◽  
Author(s):  
Michel Baum ◽  
Katherine Twombley ◽  
Jyothsna Gattineni ◽  
Catherine Joseph ◽  
Lin Wang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Proximal Tubule ◽  
Brush Border Membrane ◽  
Protein Abundance ◽  
Relative Role ◽  
Serum Bicarbonate ◽  
Adult Mice ◽  
Lower Blood ◽  
Blood Pressures

NHE3 is the predominant Na+/H+ exchanger on the brush-border membrane (BBM) of the proximal tubule in adults. However, NHE3 null mice still have significant renal BBM Na+/H+ activity. NHE8 has been localized to the BBM of proximal tubules and is more highly expressed in neonates than adult animals. The relative role of NHE8 in adult renal H+ transport is unclear. This study examined whether there was compensation by NHE8 in NHE3−/− mice and by NHE3 in NHE8−/− mice. NHE3−/− mice had significant metabolic acidosis, and renal BBM NHE8 protein abundance was greater in NHE3−/− mice than control mice, indicating that there may be compensation by NHE8 in NHE3−/− mice. NHE8−/− mice had serum bicarbonate levels and pH that were not different from controls. NHE3 protein expression on the BBM was greater in NHE8−/− mice than in wild-type mice, indicating that there may be compensation by NHE3 in NHE8−/− mice. Both BBM NHE3 and NHE8 protein abundance increased in response to acidosis. Blood pressure and Na+/H+ exchanger activity were comparable in NHE8−/− mice to that of controls, but both were significantly lower in NHE3−/− mice compared with control mice. Compared with NHE3−/− mice, NHE3−/−/NHE8−/− mice had lower blood pressures. While serum bicarbonate was comparable in NHE3−/− mice and NHE3−/−/NHE8−/− mice, proximal tubule Na+/H+ exchange activity was less in NHE3−/−/NHE8−/− mice compared with NHE3−/− mice. In conclusion, NHE3 is the predominant Na+/H+ exchanger in adult mice. NHE8 may play a compensatory role in renal acidification and blood pressure regulation in NHE3−/− mice.

scholarly journals Maturation of the Na+/H+ antiporter (NHE3) in the proximal tubule of the hypothyroid adrenalectomized rat

2004 ◽  
Vol 287 (3) ◽  
pp. F521-F527 ◽  
Author(s):  
Neena Gupta ◽  
Vangipuram Dwarakanath ◽  
Michel Baum
Keyword(s):  
Proximal Tubule ◽  
Brush Border Membrane ◽  
Mrna Abundance ◽  
Protein Abundance ◽  
Sprague Dawley ◽  
Sham Control ◽  
Sprague Dawley Rats ◽  
Sodium Dependent ◽  
Combined Deficiency

In previous studies examining the role of glucocorticoids and thyroid hormone on the maturation of the Na+/H+ antiporter (NHE3), we found attenuation in the maturational increase in proximal tubule apical Na+/H+ antiporter activity but no change in NHE3 mRNA abundance in either glucocorticoid-deficient or hypothyroid rats. In addition, prevention of the maturational increase in either hormone failed to totally prevent the maturational increase in Na+/H+ antiporter activity. We hypothesized that one hormone played a compensatory role when the other was deficient. The present study examined whether combined deficiency of thyroid and glucocorticoid hormones would completely prevent the maturation of the Na+/H+ antiporter. Adrenalectomy was performed in 9-day-old hypothyroid Sprague-Dawley rats, a time before the normal postnatal maturational increase in these hormones occurs. Nine- and 30-day-old adrenalectomized (ADX), hypothyroid rats had comparable NHE3 mRNA abundance, which was 5- to 10-fold less than 30-day-old ADX, hypothyroid rats that received corticosterone-thyroxine replacement and 30-day-old sham control rats ( P < 0.05). Brush-border membrane NHE3 protein abundance was comparable in 9- and 30-day-old ADX, hypothyroid groups and ∼20-fold lower than both the 30-day replacement and 30-day sham groups ( P < 0.05). Similarly, the replacement and sham groups had higher sodium-dependent proton secretion than 9- and 30-day-old ADX, hypothyroid groups ( P < 0.05). We conclude that combined deficiency of both hormones totally prevents the maturational increase in NHE3 mRNA and protein abundance and Na+/H+ antiporter activity.

Blood pressure maintenance in NHE3-deficient mice with transgenic expression of NHE3 in small intestine

2005 ◽  
Vol 288 (3) ◽  
pp. R685-R691 ◽  
Author(s):  
William T. Noonan ◽  
Alison L. Woo ◽  
Michelle L. Nieman ◽  
Vikram Prasad ◽  
Patrick J. Schultheis ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Small Intestine ◽  
Transgenic Expression ◽  
Specific Effects ◽  
Lower Blood ◽  
Blood Pressures ◽  
Pressure Natriuresis ◽  
Deficient Mice ◽  
Robust Response

NHE3 Na+/H+ exchanger knockout ( Nhe3−/−) mice have severe absorptive deficits in the kidney proximal tubule and intestinal tract. The resulting hypovolemia has confounded efforts to carefully evaluate the specific effects of NHE3 deficiency on kidney function. Development of mice with transgenic expression of NHE3 in the small intestine (tg Nhe3−/−) has allowed us to analyze the role of renal NHE3 in overall maintenance of blood pressure, pressure natriuresis, and autoregulation of both glomerular filtration rate (GFR) and renal blood flow (RBF). Ambulatory blood pressure, measured by telemetry, was lower in tg Nhe3−/− mice than in wild-type controls (tg Nhe3+/+) when the mice were maintained on a normal NaCl diet but was normalized when they were provided with a high NaCl intake. Furthermore, administration of the AT1-receptor blocker losartan showed that circulating ANG II plays a major role in maintaining blood pressure in tg Nhe3−/− mice fed normal NaCl but not in those receiving high NaCl. Clearance studies revealed a blunted pressure-natriuresis response in tg Nhe3−/− mice at lower blood pressures but a robust response at higher blood pressures. Autoregulation of GFR and RBF was normal in tg Nhe3−/− mice. These results show that dietary NaCl loading normalizes blood pressure in awake tg Nhe3−/− mice and that alterations in NHE3 activity are not essential for normal autoregulation of GFR and RBF. Furthermore, the data strongly support the hypothesis that NHE3 plays an important role in the diuretic and natriuretic responses to increases in blood pressure but also show that mechanisms not involving NHE3 mediate pressure natriuresis in the higher range of blood pressures studied.

scholarly journals Characterization of renal NaCl and oxalate transport in Slc26a6−/− mice

2019 ◽  
Vol 316 (1) ◽  
pp. F128-F133 ◽  
Author(s):  
Felix Knauf ◽  
Heino Velazquez ◽  
Victoria Pfann ◽  
Zhirong Jiang ◽  
Peter S. Aronson
Keyword(s):  
Blood Pressure ◽  
Proximal Tubule ◽  
Fractional Excretion ◽  
Wild Type ◽  
Nacl Transport ◽  
Lower Blood ◽  
Urine Oxalate

The apical membrane Cl−/oxalate exchanger SLC26A6 has been demonstrated to play a role in proximal tubule NaCl transport based on studies in microperfused tubules. The present study is directed at characterizing the role of SLC26A6 in NaCl homeostasis in vivo under physiological conditions. Free-flow micropuncture studies revealed that volume and Cl− absorption were similar in surface proximal tubules of wild-type and Slc26a6−/− mice. Moreover, the increments in urine flow rate and sodium excretion following thiazide and furosemide infusion were identical in wild-type and Slc26a6−/− mice, indicating no difference in NaCl delivery out of the proximal tubule. The absence of an effect of deletion of SLC26A6 on NaCl homeostasis was further supported by the absence of lower blood pressure in Slc26a6−/− compared with wild-type mice on normal or low-salt diets. Moreover, raising plasma and urine oxalate by feeding mice a diet enriched in soluble oxalate did not affect mean blood pressure. In contrast to the lack of effect of SLC26A6 deletion on NaCl homeostasis, fractional excretion of oxalate was reduced from 1.6 in wild-type mice to 0.7 in Slc26a6−/− mice. We conclude that, although SLC26A6 is dispensable for renal NaCl homeostasis, it is required for net renal secretion of oxalate.

scholarly journals Effect of metabolic acidosis on neonatal proximal tubule acidification

2010 ◽  
Vol 299 (5) ◽  
pp. R1360-R1368 ◽  
Author(s):  
Katherine Twombley ◽  
Jyothsna Gattineni ◽  
Ion Alexandru Bobulescu ◽  
Vangipuram Dwarakanath ◽  
Michel Baum
Keyword(s):  
Metabolic Acidosis ◽  
Proximal Tubule ◽  
Brush Border ◽  
Brush Border Membrane ◽  
Membrane Vesicles ◽  
Protein Abundance ◽  
Serum Bicarbonate ◽  
Neonatal Rats ◽  
Neonatal Mice ◽  
Maximal Capacity

The serum bicarbonate in neonates is lower than adults due in large part to a lower rate of proximal tubule acidification. It is unclear if the neonatal proximal tubule is functioning at maximal capacity or if the proximal tubule can respond to metabolic acidosis as has been described in adult proximal tubules. We find that neonatal mouse brush-border membranes have a lower Na+/H+ exchanger (NHE) 3 protein abundance (neonate 0.11 ± 0.05 vs. adult 0.64 ± 0.07; P < 0.05) and a higher NHE8 protein abundance (neonate 1.0 ± 0.01 vs. adult 0.13 ± 0.09; P < 0.001) compared with adults. To examine if neonates can adapt to acidosis, neonatal mice were gavaged with either acid or vehicle for 4 days, resulting in a drop in serum bicarbonate from 19.5 ± 1.0 to 8.9 ± 0.6 meq/l ( P < 0.001). Proximal convoluted tubule Na+/H+ exchanger activity (dpHi/d t) was 1.68 ± 0.19 pH units/min in control tubules and 2.49 ± 0.60 pH units/min in acidemic neonatal mice ( P < 0.05), indicating that the neonatal proximal tubule can respond to metabolic acidosis with an increase in Na+/H+ exchanger activity. Similarly, brush-border membrane vesicles from neonatal rats had an increase in Na+/H+ exchanger activity with acidemia that was almost totally inhibited by 10−6 M 5-( N-ethyl- n-isopropyl)-amiloride, a dose that has little effect on NHE3 but inhibits NHE8. There was a significant increase in both NHE3 (vehicle 0.35 ± 0.07 vs. acid 0.73 ± 0.07; P < 0.003) and NHE8 brush-border membrane protein abundance (vehicle 0.41 ± 0.05 vs. acid 0.73 ± 0.06; P < 0.001) in acidemic mouse neonates compared with controls. A comparable increase in NHE3 and NHE8 was found in neonatal rats with acidosis. In conclusion, the neonatal proximal tubule can adapt to metabolic acidosis with an increase in Na+/H+ exchanger activity.

Role of Autonomic Nervous System in Maintenance of Cerebral and Renal Hypertension

1957 ◽  
Vol 188 (2) ◽  
pp. 371-374 ◽  
Author(s):  
Sol Rothman ◽  
Douglas R. Drury
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Autonomic Nervous System ◽  
Renal Hypertension ◽  
The Other ◽  
Peripheral Vasculature ◽  
Blood Pressures ◽  
Sympathetic Nervous ◽  
Blood Pressure Responses

The blood pressure responses to various drugs were investigated in renal hypertensive, cerebral hypertensive and normotensive rabbits. Hexamethonium bromide and Dibenamine reduced the blood pressures of renal and cerebral hypertensives. Effects in the normal were insignificant. The cerebral hypertensive's blood pressure was slightly affected by benzodioxane. Blood pressure was not reduced at all in the other groups. Blood pressure of the renal hypertensive rabbit was greatly reduced by Veriloid and dihydroergocornine. Blood pressures of cerebral and normal animals were affected to a lesser degree. The results suggest that maintenance of hypertension in the cerebral hypertensive rabbit depends on an overactive sympathetic nervous system, possibly due to the release of medullary pressor centers from inhibitory impulses originating in higher centers; whereas, the maintenance of hypertension in the renal hypertensive rabbit may be attributed to an increased reactivity of the peripheral vasculature to a normal sympathetic tone.

Physical exercise and blood pressure with reference to the angiotensinogen M235T polymorphism

2002 ◽  
Vol 10 (2) ◽  
pp. 71-77 ◽  
Author(s):  
Rainer Rauramaa ◽  
Raimo Kuhanen ◽  
Timo A. Lakka ◽  
Sari B. Väisänen ◽  
Pirjo Halonen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Reference Group ◽  
Controlled Trial ◽  
Exercise Group ◽  
Moderate Intensity ◽  
Moderate Intensity Exercise ◽  
Blood Pressures ◽  
Agt Gene ◽  
M235t Polymorphism

We investigated the role of the angiotensinogen (AGT) gene M235T polymorphism in determining blood pressure (BP) response to moderate intensity exercise in a 6-yr randomized controlled trial in 140 middle-aged men. Sitting, supine, and standing blood pressures were measured annually. Of the randomized men, 86% participated in the trial for 6 yr. Submaximal cardiorespiratory fitness increased by 16% in the exercise group. In the M homozygotes, sitting systolic BP decreased by 1.0 mmHg in the exercise but increased by 14.6 mmHg in the reference group ( P = 0.007 for net effect). Sitting and supine diastolic BP decreased by 6.2 and 3.3 mmHg in the exercise but increased by 2.8 and 3.2 mmHg in the reference group ( P = 0.026 and 0.024 for net effects), respectively. Regular moderate intensity exercise attenuates aging-related increase in systolic BP and decreases diastolic BP among the M homozygotes of the AGT gene M235T polymorphism.

scholarly journals Differential regulation of the renal sodium-phosphate cotransporters NaPi-IIa, NaPi-IIc, and PiT-2 in dietary potassium deficiency

2009 ◽  
Vol 297 (2) ◽  
pp. F350-F361 ◽  
Author(s):  
Sophia Y. Breusegem ◽  
Hideaki Takahashi ◽  
Hector Giral-Arnal ◽  
Xiaoxin Wang ◽  
Tao Jiang ◽  
...  
Keyword(s):  
Brush Border Membrane ◽  
Protein Abundance ◽  
Transport Activity ◽  
Renal Brush Border Membrane ◽  
Cytoplasmic Vesicles ◽  
Dietary Potassium ◽  
Proximal Tubular ◽  
K Deficiency ◽  
Altered Lipid

Dietary potassium (K) deficiency is accompanied by phosphaturia and decreased renal brush border membrane (BBM) vesicle sodium (Na)-dependent phosphate (Pi) transport activity. Our laboratory previously showed that K deficiency in rats leads to increased abundance in the proximal tubule BBM of the apical Na-Pi cotransporter NaPi-IIa, but that the activity, diffusion, and clustering of NaPi-IIa could be modulated by the altered lipid composition of the K-deficient BBM (Zajicek HK, Wang H, Puttaparthi K, Halaihel N, Markovich D, Shayman J, Beliveau R, Wilson P, Rogers T, Levi M. Kidney Int 60: 694–704, 2001; Inoue M, Digman MA, Cheng M, Breusegem SY, Halaihel N, Sorribas V, Mantulin WW, Gratton E, Barry NP, Levi M. J Biol Chem 279: 49160–49171, 2004). Here we investigated the role of the renal Na-Pi cotransporters NaPi-IIc and PiT-2 in K deficiency. Using Western blotting, immunofluorescence, and quantitative real-time PCR, we found that, in rats and in mice, K deficiency is associated with a dramatic decrease in the NaPi-IIc protein abundance in proximal tubular BBM and in NaPi-IIc mRNA. In addition, we documented the presence of a third Na-coupled Pi transporter in the renal BBM, PiT-2, whose abundance is also decreased by dietary K deficiency in rats and in mice. Finally, electron microscopy showed subcellular redistribution of NaPi-IIc in K deficiency: in control rats, NaPi-IIc immunolabel was primarily in BBM microvilli, whereas, in K-deficient rats, NaPi-IIc BBM label was reduced, and immunolabel was prevalent in cytoplasmic vesicles. In summary, our results demonstrate that decreases in BBM abundance of the phosphate transporter NaPi-IIc and also PiT-2 might contribute to the phosphaturia of dietary K deficiency, and that the three renal BBM phosphate transporters characterized so far can be differentially regulated by dietary perturbations.

scholarly journals Genetic and genomic evidence for an important role of the Na+/H+ exchanger 3 in blood pressure regulation and angiotensin II-induced hypertension

2019 ◽  
Vol 51 (4) ◽  
pp. 97-108 ◽  
Author(s):  
Xiao C. Li ◽  
Xiaowen Zheng ◽  
Xu Chen ◽  
Chunling Zhao ◽  
Dongmin Zhu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Proximal Tubules ◽  
Ang Ii ◽  
Pressure Regulation ◽  
Blood Pressure Homeostasis ◽  
Induced Hypertension ◽  
Basal Blood Pressure

The sodium (Na+)/hydrogen (H+) exchanger 3 (NHE3) and sodium-potassium adenosine triphosphatase (Na+/K+-ATPase) are two of the most important Na+ transporters in the proximal tubules of the kidney. On the apical membrane side, NHE3 primarily mediates the entry of Na+ into and the exit of H+ from the proximal tubules, directly and indirectly being responsible for reabsorbing ~50% of filtered Na+ in the proximal tubules of the kidney. On the basolateral membrane side, Na+/K+-ATPase serves as a powerful engine driving Na+ out of, while pumping K+ into the proximal tubules against their concentration gradients. While the roles of NHE3 and Na+/K+-ATPase in proximal tubular Na+ transport under in vitro conditions are well recognized, their respective contributions to the basal blood pressure regulation and angiotensin II (ANG II)-induced hypertension remain poorly understood. Recently, we have been fortunate to be able to use genetically modified mouse models with global, kidney- or proximal tubule-specific deletion of NHE3 to directly determine the cause and effect relationship between NHE3, basal blood pressure homeostasis, and ANG II-induced hypertension at the whole body, kidney and/or proximal tubule levels. The purpose of this article is to review the genetic and genomic evidence for an important role of NHE3 with a focus in the regulation of basal blood pressure and ANG II-induced hypertension, as we learned from studies using global, kidney- or proximal tubule-specific NHE3 knockout mice. We hypothesize that NHE3 in the proximal tubules is necessary for maintaining basal blood pressure homeostasis and the development of ANG II-induced hypertension.

Accuracy of the London School of Hygiene and Remler M2000 sphygmomanometers

1981 ◽  
Vol 61 (s7) ◽  
pp. 399s-401s ◽  
Author(s):  
D. J. Fitzgerald ◽  
W. G. O'Callaghan ◽  
K. O'Malley ◽  
E. T. O'Brien
Keyword(s):  
Blood Pressure ◽  
Pressure Measurement ◽  
Blood Pressure Measurement ◽  
Calibration Error ◽  
London School ◽  
Lower Blood ◽  
Significant Difference ◽  
Blood Pressures ◽  
The Mean ◽  
Selection Of

1. The accuracy of the Remler M2000, a semiautomatic portable blood pressure recorder, was assessed with the London School of Hygiene (LSH) and Hawkesley random-zero sphygmomanometers used as reference standards. 2. The Remler gave higher recordings than the LSH sphygmomanometer, the mean systolic and diastolic differences being 5.9 mmHg (P &lt; 0.001) and 4.7 mmHg (P &lt; 0.001) respectively. No significant difference was demonstrated between paired Remler and Hawkesley recordings. 3. When simultaneous paired LSH and Hawkesley sphygmomanometer recordings were compared, the LSH gave lower blood pressures: 7.1 mmHg (P &lt; 0.001) for systolic and 3.6 mmHg (P &lt; 0.001) for diastolic recordings. 4. The LSH sphygmomanometer underestimates blood pressure, partly due to a calibration error but also because the selection of end points for this device differs from other methods of blood pressure measurement.

The Relationship between Religious Activities and Blood Pressure in Older Adults

1998 ◽  
Vol 28 (2) ◽  
pp. 189-213 ◽  
Author(s):  
Harold G. Koenig ◽  
Linda K. George ◽  
Judith C. Hays ◽  
David B. Larson ◽  
Harvey J. Cohen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Older Adults ◽  
High Blood Pressure ◽  
Religious Activity ◽  
Religious Activities ◽  
The Bible ◽  
Lower Blood ◽  
Religious Services ◽  
Blood Pressures ◽  
The Relationship

Objective: To examine the relationship between religious activities and blood pressure in community-dwelling older adults. Method: Blood pressure and religious activities were assessed in a probability sample of 3,963 persons age sixty-five years or older participating in the Duke EPESE survey. Participants were asked if their doctor had ever informed them that they had high blood pressure and if they were currently taking medication for high blood pressure. After the interview, systolic and diastolic blood pressures were measured following a standardized protocol. Data were available for three waves of the survey (1986, 1989–90, and 1993–94). Analyses were stratified by age (65–74 vs. over 75) and by race (Whites vs. Blacks) and were controlled for age, race, gender, education, physical functioning, body mass index, and, in longitudinal analyses, blood pressure from the previous wave. Results: Cross-sectional analyses revealed small (1–4 mm Hg) but consistent differences in measured systolic and diastolic blood pressures between frequent (once/wk) and infrequent (< once/wk) religious service attenders. Lower blood pressures were also observed among those who frequently prayed or studied the Bible (daily or more often). Blood pressure differences were particularly notable in Black and younger elderly, in whom religious activity at one wave predicted blood pressures three years later. Among participants who both attended religious services and prayed or studied the Bible frequently, the likelihood of having a diastolic blood pressure of 90 mm Hg or higher was 40 percent lower than found in participants who attended religious services infrequently and prayed or studied the Bible infrequently (OR 0.60, 95% CI, 0.48–0.75, p < .0001). Among participants told they had high blood pressure, religiously active persons were more likely to be taking their blood pressure medication; this could not, however, explain the differences in blood pressure observed. While most religious activity was associated with lower blood pressure, those who frequently watched religious TV or listened to religious radio actually had higher blood pressures. Conclusions: Religiously active older adults tend to have lower blood pressures than those who are less active. This applies to attendance at religious services and private religious activities, but not to religious media. Physiological mechanisms are discussed.

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