Salt-resistant blood pressure and salt-sensitive renal autoregulation in chronic streptozotocin diabetes

2009 ◽  
Vol 296 (6) ◽  
pp. R1761-R1770 ◽  
Author(s):  
Catherine Lau ◽  
Ian Sudbury ◽  
Michael Thomson ◽  
Perry L. Howard ◽  
Alex B. Magil ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Salt Intake ◽  
Collecting Duct ◽  
Periodic Acid ◽  
Systolic Pressure ◽  
Diabetic Rats ◽  
Tubuloglomerular Feedback ◽  
Dietary Salt ◽  
Periodic Acid Schiff ◽  
High Salt Intake

Hyperfiltration occurs in early type 1 diabetes mellitus in both rats and humans. It results from afferent vasodilation and thus may impair stabilization of glomerular capillary pressure by autoregulation. It is inversely related to dietary salt intake, the “salt paradox.” Restoration of normal glomerular filtration rate (GFR) involves increased preglomerular resistance, probably mediated by tubuloglomerular feedback (TGF). To begin to test whether the salt paradox has pathogenic significance, we compared intact vs. diabetic (streptozotocin) Long-Evans rats with normal and increased salt intake, 1 and ∼3% by weight of food eaten, respectively. Weekly 24-h blood pressure records were acquired by telemetry before and during diabetes. Blood glucose was maintained at ∼20 mmol/l by insulin implants. GFR was significantly elevated only in diabetic rats on normal salt intake, confirming diabetic hyperfiltration and the salt paradox. Renal blood flow dynamics show strong contributions to autoregulation by both TGF and the myogenic mechanism and were not impaired by diabetes or by increased salt intake. Separately, systolic pressure was not elevated in diabetic rats at any time during 12 wk with normal or high salt intake. Autoregulation was effective in all groups, and the diabetic-normal salt group showed significantly improved autoregulation at low perfusion pressures. Histological examination revealed very minor glomerulosclerosis and modest mesangial expansion, although neither was diagnostic of diabetes. Periodic acid-Schiff-positive droplets found in distal tubules and collecting duct segments were diagnostic of diabetic kidneys. Biologically significant effects attributable to increased salt intake were abrogation of hyperfiltration and of the left shift in autoregulation in diabetic rats.

Blood Pressure of Alloxan Diabetic Rats at Regular and High Salt Intake

1981 ◽  
Vol 3 (3) ◽  
pp. 509-522 ◽  
Author(s):  
Friedrich C. Luft ◽  
Laura I. Rankin ◽  
Andrew P. Evan ◽  
Lynn R. Willis ◽  
Julia B. Clark
Keyword(s):  
Blood Pressure ◽  
Salt Intake ◽  
Diabetic Rats ◽  
High Salt ◽  
High Salt Intake

Abstract 42: AT1 Angiotensin Receptors in Principal Cells of the Collecting Duct Have Minimal Impact on Blood Pressure and the Development of Hypertension.

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Daian Chen ◽  
Johannes Stegbauer ◽  
Matthew A. Sparks ◽  
Donald Kohan ◽  
Susan B. Gurley ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Salt Intake ◽  
Collecting Duct ◽  
Weight Ratio ◽  
Angiotensin Receptors ◽  
Mrna Levels ◽  
Ang Ii ◽  
Mouse Line ◽  
Dietary Salt ◽  
Transgenic Mouse Line

The main actions of the renin angiotensin system to control blood pressure (BP) are mediated by the angiotensin type 1 receptors (AT 1 R). The major murine AT 1 R isoform, AT 1A is highly expressed in epithelial cells throughout the nephron, including the collecting duct (CD). The CD consists of two cell types, principal (PC) and intercalated cells (IC) with distinct functions. Activation of AT 1 R in PC stimulates solute reabsorption in the CD by increasing the activity of epithelial sodium channels. To examine the role of the AT 1A R in the PC to BP regulation and the development of hypertension in vivo , we generated inbred 129SvEv mice with cell-specific deletion of AT 1A R in PC (PC-KO, n=6). AQP2-Cre transgenic mouse line was used to excise the floxed Agtr1a allele in PC. mTmG reporter mouse line was used to confirm specific expression of AQP2-Cre transgene in PC, and found the pattern of expression to be predominantly in medullary CD. Using RT-PCR, mRNA levels for AT 1A R were reduced by ≈50% in the inner medulla of PC-KO mice ( P <0.05), but unaffected in cortex. Baseline BP measured by radiotelemetry was similar between PC-KO (122±1.6 mm Hg) and controls (122±1.6 mm Hg). During one week of feeding a low salt (<0.002% NaCl) diet, MAP fell significantly (P<0.05) and to a similar extent in both groups, (PC-KO: 116±1 mm Hg; Controls: 117±2 mm Hg). High salt (6% NaCl) diet increased BP (P<0.01), but was not different between groups (PC-KO: 129±2 mm Hg; Controls: 131±2 mm Hg). Finally, we induced hypertension with chronic infusion of Ang II (1000 ng/kg/min) by osmotic mini-pumps. During the initial phase (days 1-8), there was a modest but significant attenuation of hypertension in PC-KO (167±7 mm Hg) compared to controls (178±3 mm Hg, P<0.001). However, by day 9 levels of BP were indistinguishable between groups and there was no difference in BP in the later phase (days 9-14) of hypertension (PC-KO: 175±12 mm Hg; Controls: 177±7 mm Hg). Heart to body weight ratio after Ang II infusion was not different between groups. In summary, AT 1A R in PC of the medullary CD have little influence on BP, adaptation to changes in dietary salt intake or development of hypertension. We suggest that other mediators, such as aldosterone, may have a more important role to influence sodium handling in this nephron segment.

Links Between Dietary Salt Intake, Renal Salt Handling, Blood Pressure, and Cardiovascular Diseases

2005 ◽  
Vol 85 (2) ◽  
pp. 679-715 ◽  
Author(s):  
Pierre Meneton ◽  
Xavier Jeunemaitre ◽  
Hugh E. de Wardener ◽  
Graham A. Macgregor
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Diseases ◽  
Salt Intake ◽  
Causal Link ◽  
Left Ventricular ◽  
High Salt ◽  
Human Populations ◽  
Dietary Salt ◽  
Dietary Salt Intake ◽  
High Salt Intake

Epidemiological, migration, intervention, and genetic studies in humans and animals provide very strong evidence of a causal link between high salt intake and high blood pressure. The mechanisms by which dietary salt increases arterial pressure are not fully understood, but they seem related to the inability of the kidneys to excrete large amounts of salt. From an evolutionary viewpoint, the human species is adapted to ingest and excrete <1 g of salt per day, at least 10 times less than the average values currently observed in industrialized and urbanized countries. Independent of the rise in blood pressure, dietary salt also increases cardiac left ventricular mass, arterial thickness and stiffness, the incidence of strokes, and the severity of cardiac failure. Thus chronic exposure to a high-salt diet appears to be a major factor involved in the frequent occurrence of hypertension and cardiovascular diseases in human populations.

High dietary salt intake increases carotid blood pressure and wave reflection in normotensive healthy young men

2011 ◽  
Vol 110 (2) ◽  
pp. 468-471 ◽  
Author(s):  
Mirian J. Starmans-Kool ◽  
Alice V. Stanton ◽  
Yun Y. Xu ◽  
Simon A. McG Thom ◽  
Kim H. Parker ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Body Weight ◽  
Wave Reflection ◽  
Salt Intake ◽  
High Salt ◽  
Dietary Salt ◽  
Dietary Salt Intake ◽  
High Salt Intake ◽  
Increased Risk

Dietary salt intake is associated with high brachial blood pressure (BP) and increased risk of cardiovascular disease. We investigated whether changes in dietary salt intake are associated with changes in central BP and wave reflection in healthy volunteers. Ten healthy normotensive male volunteers (22–40 yr) participated in a 6-wk double-blind randomized crossover study to compare a low-dietary salt intake (60–80 mmol sodium/day) with a high-salt intake (low salt intake supplemented with 128 mmol sodium/day) on central BP and wave reflection. Brachial and carotid BP, carotid blood flow velocity, forward (Pf) and backward (Pb) pressure, wave intensity, body weight, and urinary electrolyte excretion were measured at the end of each crossover period. High salt intake significantly increased carotid systolic BP [98 (SD 11) vs. 91 mmHg (SD 13), P < 0.01] and increased wave reflection [ratio of backward to forward pressure (Pb/Pf) 0.13 (SD 0.02) vs. 0.11 (SD 0.03), P = 0.04] despite only small effects on brachial BP [114 (SD 9) vs. 112 mmHg (SD 6), P = 0.1]. Urinary sodium excretion and body weight were also increased following high salt intake. High salt intake disproportionately increases central BP compared with brachial BP as a result of enhanced wave reflection. These effects may contribute to the adverse effect of high dietary salt intake on the risk of cardiovascular disease.

Dietary salt decreases cytosolic calcium in platelets from Dahl salt-sensitive rats

1995 ◽  
Vol 269 (5) ◽  
pp. R1225-R1229 ◽  
Author(s):  
T. Ishida ◽  
M. Ishida ◽  
H. Matsuura ◽  
R. Ozono ◽  
G. Kajiyama ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Salt Intake ◽  
Cytosolic Calcium ◽  
High Salt ◽  
Dietary Salt ◽  
Fura 2 ◽  
High Salt Intake ◽  
Induced Hypertension

To determine whether abnormal cellular Ca2+ handling is involved in salt-induced hypertension of Dahl salt-sensitive rats (DS), we investigated Ca2+ handling in fura 2-loaded platelets of DS and Dahl salt-resistant rats (DR) fed a high-NaCl (8%) or a low-NacL (0.3%) diet for 4 wk from 5 wk of age. At 5 wk of age, blood pressure, resting cytosolic Ca2+ concentration ([Ca2+]i), the thrombin-evoked increase in [Ca2+]i and the size of internal Ca2+ stores of DS were comparable with those of DR. After 4 wk on the diets, resting [Ca2+]i of DS on high-NaCl diet was lower than that of DS on low-NaCl diet, and there was no effect of high salt intake on resting [Ca2+]i in DR. In DS, high salt intake attenuated the [Ca2+]i response to thrombin in the presence of external Ca2+. In contrast, the [Ca2+]i response to thrombin in the absence of external Ca2+ was enhanced by high salt intake in DS. The size of internal Ca2+ stores was increased by high salt intake in DS but not in DR. These data suggest that it is not obligatory for hypertension to be accompanied by an increase in platelet [Ca2+]i.

scholarly journals Knowledge of Salt intake and Blood Pressure Control among Hypertensive Patients in a Tertiary Hospital

2019 ◽  
Vol 2 (1) ◽  
pp. 14-18
Author(s):  
A O Adeagbo ◽  
O E Omosanya ◽  
A O Ayodapo ◽  
O T Elegbede ◽  
O M Shabi
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Control ◽  
Salt Intake ◽  
Daily Intake ◽  
Pressure Control ◽  
High Salt ◽  
Dietary Salt ◽  
Cross Sectional ◽  
Hypertensive Patients ◽  
High Salt Intake

As the prevalence of hypertension increases in adult Nigerians, achieving target blood pressure (BP) control has become an important management challenge. High salt intake is an important risk factor for hypertension and its high intake prevents adequate BP control. This study aims to explore the knowledge of salt intake and blood pressure control among hypertensive patients. Data were collected from a cross-sectional sample involving 564 adult hypertensive patients that were followed for at least 3 months prior to recruitment to this study. Data collection comprised interviewer-administered structured questionnaires about demographics, knowledge and practices related to salt, followed by measurement of blood pressure. A majority (92.9%) of the respondents knew that eating too much salt could affect health and less than one-half (40.1%) actually knew that not more than one teaspoon of salt should be consumed daily. Nearly all respondents (516) knew high BP to be a possible consequence of high salt intake. Among those that took a lot of salty food, 87.7% and 78.5% had high systolic BP and diastolic BP respectively. Although the majority of respondents were knowledgeable about the adverse effects of salt, few knew the daily intake recommended value. The higher the dietary salt intake, the higher the chances of having poor BP control. Increased knowledge about recommended salt intake and individual guidance could be important for reducing salt intake in hypertensive patients.

scholarly journals Adenosine inhibits the basolateral Cl− ClC-K2/b channel in collecting duct intercalated cells

2020 ◽  
Vol 318 (4) ◽  
pp. F870-F877
Author(s):  
Oleg Zaika ◽  
Viktor N. Tomilin ◽  
Oleh Pochynyuk
Keyword(s):  
Salt Intake ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Inhibitory Effect ◽  
Intercalated Cells ◽  
Dietary Salt ◽  
Open Probability ◽  
Salt Loading ◽  
Principal Cells ◽  
High Salt Intake

Adenosine plays an important role in various aspects of kidney physiology, but the specific targets and mechanisms of actions are not completely understood. The collecting duct has the highest expression of adenosine receptors, particularly adenosine A1 receptors (A1Rs). Interstitial adenosine levels are greatly increased up to a micromolar range in response to dietary salt loading. We have previously shown that the basolateral membrane of principal cells has primarily K+ conductance mediated by Kir4.1/5.1 channels to mediate K+ recycling and to set up a favorable driving force for Na+/K+ exchange ( 47 ). Intercalated cells express the Cl− ClC-K2/b channel mediating transcellular Cl− reabsorption. Using patch-clamp electrophysiology in freshly isolated mouse collecting ducts, we found that acute application of adenosine reversely inhibits ClC-K2/b open probability from 0.31 ± 0.04 to 0.17 ± 0.06 and to 0.10 ± 0.05 for 1 and 10 µM, respectively. In contrast, adenosine (10 µM) had no measureable effect on Kir4.1/5.1 channel activity in principal cells. The inhibitory effect of adenosine on ClC-K2/b was abolished in the presence of the A1R blocker 8-cyclopentyl-1,3-dipropylxanthine (10 µM). Consistently, application of the A1R agonist N6-cyclohexyladenosine (1 µM) recapitulated the inhibitory action of adenosine on ClC-K2/b open probability. The effects of adenosine signaling in the collecting duct were independent from its purinergic counterpartner, ATP, having no measurable actions on ClC-K2/b and Kir4.1/5.1. Overall, we demonstrated that adenosine selectively inhibits ClC-K2/b activity in intercalated cells by targeting A1Rs. We propose that inhibition of transcellular Cl− reabsorption in the collecting duct by adenosine would aid in augmenting NaCl excretion during high salt intake.

Macula densa basolateral ATP release is regulated by luminal [NaCl] and dietary salt intake

2004 ◽  
Vol 286 (6) ◽  
pp. F1054-F1058 ◽  
Author(s):  
Peter Komlosi ◽  
Janos Peti-Peterdi ◽  
Amanda L. Fuson ◽  
Attila Fintha ◽  
Laszlo Rosivall ◽  
...  
Keyword(s):  
Salt Intake ◽  
Mesangial Cells ◽  
Basolateral Membrane ◽  
Atp Release ◽  
Macula Densa ◽  
Tubuloglomerular Feedback ◽  
Thick Ascending Limb ◽  
Dietary Salt ◽  
Dietary Salt Intake ◽  
High Salt Intake

One component of the macula densa (MD) tubuloglomerular feedback (TGF) signaling pathway may involve basolateral release of ATP through a maxi-anion channel. Release of ATP has previously been studied during a maximal luminal NaCl concentration ([NaCl]L) stimulus (20–150 mmol/l). Whether MD ATP release occurs during changes in [NaCl]L within the physiological range (20–60 mmol/l) has not been examined. Also, because TGF is known to be enhanced by low dietary salt intake, we examined the pattern of MD ATP release from salt-restricted rabbits. Fluorescence microscopy, with fura 2-loaded cultured mouse mesangial cells as biosensors, was used to assess ATP release from the isolated, perfused thick ascending limb containing the MD segment. The mesangial biosensor cells, which contain purinergic receptors and elevate intracellular Ca2+ concentration ([Ca2+]i) on ATP binding, were placed adjacent to the MD basolateral membrane. Elevations in [NaCl]L between 0 and 80 mmol/l, in 20-mmol/l increments, caused stepwise increases in [Ca2+]i, with the highest increase at [NaCl]L of ∼60 mmol/l. Luminal furosemide at 10−4 mol/l blocked ATP release, which suggests that the efflux of ATP required MD Na-2Cl-K cotransport. A low-salt diet for 1 wk increased the magnitude of [NaCl]L-dependent elevations in biosensor [Ca2+]i by twofold, whereas high-salt intake had no effect. In summary, ATP release occurs over the same range of [NaCl]L (20–60 mmol/l) previously reported for TGF responses, and, similar to TGF, ATP release was enhanced by dietary salt restriction. Thus these two findings are consistent with the role of MD ATP release as a signaling component of the TGF pathway.

scholarly journals Role of renal transporters and novel regulatory interactions in the TAL that control blood pressure

2017 ◽  
Vol 49 (5) ◽  
pp. 261-276 ◽  
Author(s):  
Lesley A. Graham ◽  
Anna F. Dominiczak ◽  
Nicholas R. Ferreri
Keyword(s):  
Blood Pressure ◽  
Salt Intake ◽  
Salt Sensitivity ◽  
Public Health Issue ◽  
Thick Ascending Limb ◽  
Dietary Salt ◽  
Therapeutic Application ◽  
Dietary Salt Intake ◽  
Renal Transporters ◽  
High Salt Intake

Hypertension (HTN), a major public health issue is currently the leading factor in the global burden of disease, where associated complications account for 9.4 million deaths worldwide every year. Excessive dietary salt intake is among the environmental factors that contribute to HTN, known as salt sensitivity. The heterogeneity of salt sensitivity and the multiple mechanisms that link high salt intake to increases in blood pressure are of upmost importance for therapeutic application. A continual increase in the kidney’s reabsorption of sodium (Na+) relies on sequential actions at various segments along the nephron. When the distal segments of the nephron fail to regulate Na+, the effects on Na+ homeostasis are unfavorable. We propose that the specific nephron region where increased active uptake occurs as a result of variations in Na+ reabsorption is at the thick ascending limb of the loop of Henle (TAL). The purpose of this review is to urge the consideration of the TAL as contributing to the pathophysiology of salt-sensitive HTN. Further research in this area will enable development of a therapeutic application for targeted treatment.

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