Faculty Opinions recommendation of Connexin 30 deficiency impairs renal tubular ATP release and pressure natriuresis.

Flow-induced cytosolic Ca2+ Cai2+ signaling in renal tubular epithelial cells is mediated in part through P2 receptor (P2R) activation by locally released ATP. The ability of P2R to regulate salt and water reabsorption has suggested a possible contribution of ATP release and paracrine P2R activation to cystogenesis and/or enlargement in autosomal dominant polycystic kidney disease (ADPKD). We and others have demonstrated in human ADPKD cyst cells the absence of flow-induced Cai2+ signaling exhibited by normal renal epithelial cells. We now extend these findings to primary and telomerase-immortalized normal and ADPKD epithelial cells of different genotype and of both proximal and distal origins. Flow-induced elevation of Cai2+ concentration ([Ca2+]i) was absent from ADPKD cyst cells, but in normal cells was mediated by flow-sensitive ATP release and paracrine P2R activation, modulated by ecto-nucleotidase activity, and abrogated by P2R inhibition or extracellular ATP hydrolysis. In contrast to the elevated ATP release from ADPKD cells in static isotonic conditions or in hypotonic conditions, flow-induced ATP release from cyst cells was lower than from normal cells. Extracellular ATP rapidly reduced thapsigargin-elevated [Ca2+]i in both ADPKD cyst and normal cells, but cyst cells lacked the subsequent, slow, oxidized ATP-sensitive [Ca2+]i recovery present in normal cells. Telomerase-immortalized cyst cells also exhibited altered CD39 and P2X7 mRNA levels. Thus the loss of flow-induced, P2R-mediated Cai2+ signaling in human ADPKD cyst epithelial cells was accompanied by reduced flow-sensitive ATP release, altered purinergic regulation of store-operated Ca2+ entry, and altered expression of gene products controlling extracellular nucleotide signaling.

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Mechanisms of Obesity-Induced Hypertension

Physiology ◽

10.1152/physiologyonline.1996.11.6.255 ◽

1996 ◽

Vol 11 (6) ◽

pp. 255-261 ◽

Cited By ~ 3

Author(s):

JE Hall ◽

DH Zappe ◽

M Alonso-Galicia ◽

JP Granger ◽

MW Brands ◽

...

Keyword(s):

Nervous System ◽

Renal Medulla ◽

Tubular Reabsorption ◽

Induced Hypertension ◽

Renal Tubular Reabsorption ◽

Renal Changes ◽

Sympathetic Nervous ◽

Pressure Natriuresis ◽

Obesity Hypertension ◽

Renal Tubular

Obesity is a major cause of human essential hypertension. Recent studies point toward increased renal tubular reabsorption and abnormal renal pressure natriuresis in mediating obesity hypertension. The mechanisms for these renal changes appear to be multifactorial, including activation of the sympathetic nervous system and altered intrarenal histology, which compresses the renal medulla.

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Prenatal programming of renal sodium handling in the rat

Clinical Science ◽

10.1042/cs20080294 ◽

2009 ◽

Vol 117 (2) ◽

pp. 75-84 ◽

Cited By ~ 46

Author(s):

Saleh H. Alwasel ◽

Nick Ashton

Keyword(s):

Fractional Excretion ◽

Control Male ◽

Low Protein ◽

Subunit Expression ◽

Renal Sodium Handling ◽

Pressure Natriuresis ◽

Renal Tubular ◽

Excretion Rates ◽

Α1 Subunit

Prenatally programmed hypertension induced by maternal protein restriction is associated with increased expression of the renal tubular Na+/K+/2Cl− co-transporter (NKCC2) and the Na+/Cl− co-transporter (NCC). This has led to the suggestion that renal Na+ retention contributes to the development of hypertension in the LP rat (offspring exposed to a maternal low-protein diet in utero). However, this hypothesis has not been tested in vivo. Renal clearance measurements in hypertensive 4-week-old male and female LP rats showed that, although the glomerular filtration rate remained unaltered, urine flow (P<0.01) and urinary Na+ excretion rates (1.6±0.3 and 3.0±0.4 μmol·min−1·100 g−1 of body weight in control male and LP male respectively; P<0.001) were increased. Na+ excretion was positively correlated with mean arterial pressure in both males (P<0.01) and females (P<0.05), but neither the slope nor the intercept differed between control and LP rats. Fractional excretion of Na+ was increased in male (1.5±0.2 and 3.0±0.5% in control and LP rats respectively; P<0.001) and female LP rats, implying reduced tubular reabsorption of Na+. Western blotting and quantitative PCR showed that NKCC2 expression was increased, whereas NCC mRNA was not up-regulated. Na+/K+ ATPase α1 subunit expression did not differ from controls; however, there was a significant reduction in whole kidney pump activity (23.4±1.8 and 17.7±1.2 nmol of phosphate·μg−1 of protein·h−1 in control male and male LP rats respectively; P<0.001); immunohistochemistry showed that the α1 subunit was virtually absent from the inner medulla. The greater Na+ excretion of LP rats can be explained, in part, by a pressure–natriuresis mechanism; however, the loss of the Na+/K+ ATPase α1 subunit from the inner medulla and up-regulation of NKCC2 suggests that altered renal Na+ handling is also programmed prenatally.

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REVIEW ON MEDOVAHASROTAS AND ITS MOOLSTHANA WITH REFERENCE TO OBESITY INDUCED HYPERTENSION

November 2020 - International Ayurvedic Medical Journal ◽

10.46607/iamj2409042021 ◽

2021 ◽

Vol 9 (4) ◽

pp. 833-837

Author(s):

Jinu K Mathew ◽

Jaishree H Mhaisekar

Keyword(s):

Weight Gain ◽

Visceral Fat ◽

Visceral Adiposity ◽

Sodium Reabsorption ◽

Lumbosacral Region ◽

Suprarenal Gland ◽

Excess Weight Gain ◽

Induced Hypertension ◽

Pressure Natriuresis ◽

Renal Tubular

Excess weight gain, especially when associated with increased visceral adiposity, is a major cause of hypertension accounting 65-75% of total cases of hypertension. Increased renal tubular sodium reabsorption by the impairment in renal pressure natriuresis plays an important role in initiating obesity induced hypertension. The present study conceptually tries to substantiate the relation between moolasthana described for medovahasrotas with reference to the pathology of obesity induced hypertension. The moola explained for medovahasrotas are Kati, Vrikka, Vapavahana and Mamsa (Kidney, Suprarenal gland, Lumbosacral region, Superficial fat) which are the general regions of deposition of visceral fat or meda. The increased meda will hamper the renal pressure natriuresis in mainly three ways: 1)Physical compression of the kidneys by fat in and around kidney. 2)Increased activation of RAAS. 3)Increased SNS activity. Thus, medovaha srotodushti further enhances medodhatudushti (Obesity or Sthoulyata) itself, which in turn destroys the srotomoola. Hence, evidence of inherent relation among medovaha srotas and its respective srotomoola is established. Keywords: Medovahasrotas, Srotomoola, obesity induced hypertension

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Proximal Renal Tubular Pressure-Natriuresis-Relation in Essential Hypertensives Following Acute Vasodilatation

Blood Pressure ◽

10.3109/08037059309077525 ◽

1993 ◽

Vol 2 (1) ◽

pp. 40-45 ◽

Cited By ~ 3

Author(s):

Lars Romer Krusell ◽

Lennard Tang Jespersen ◽

Klaus Thomsen ◽

Ole Lederballe Pedersen

Keyword(s):

Pressure Natriuresis ◽

Renal Tubular

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The acute pressure natriuresis response is suppressed by selective ETA receptor blockade

Clinical Science ◽

10.1042/cs20210937 ◽

2021 ◽

Author(s):

Geoffrey Culshaw ◽

David Binnie ◽

Neeraj Dhaun ◽

Patrick Hadoke ◽

Matthew Bailey ◽

...

Keyword(s):

Vascular Function ◽

Water Retention ◽

Salt Intake ◽

Separate Experiment ◽

Receptor Subtypes ◽

Sodium Retention ◽

Sprague Dawley ◽

Water Excretion ◽

Pressure Natriuresis ◽

Renal Tubular

Hypertension is a major risk factor for cardiovascular disease. In a significant minority of people, it develops when salt intake is increased (salt-sensitivity). It is not clear whether this represents impaired vascular function or disruption to the relationship between blood pressure (BP) and renal salt-handling (pressure natriuresis, PN). Endothelin-1 (ET-1) regulates BP via ETA and ETB receptor subtypes. Blockade of ETA receptors reduces BP, but promotes sodium retention by an unknown mechanism. ETB blockade increases both BP and sodium retention. We hypothesised that ETA blockade promotes sodium and water retention by suppressing PN. We also investigated whether suppression of PN might reflect off-target ETB blockade. Acute PN was induced by sequential arterial ligation in male Sprague Dawley rats. Intravenous atrasentan (ETA antagonist, 5mg/kg) halved the normal increase in medullary perfusion and reduced sodium and water excretion by >60%. This was not due to off-target ETB blockade because intravenous A-192621 (ETB antagonist, 10mg/kg) increased natriuresis by 50% without modifying medullary perfusion. In a separate experiment in salt-loaded rats monitored by radiotelemetry, oral atrasentan reduced systolic and diastolic BP by ~10mmHg, but additional oral A-192621 reversed these effects. Endogenous ETA stimulation has natriuretic effects mediated by renal vascular dilation while endogenous ETB stimulation in the kidney has antinatriuretic effects via renal tubular mechanisms. Pharmacological manipulation of vascular function with ET antagonists modifies the BP set-point, but even highly selective ETA antagonists attenuate PN, which may be associated with salt and water retention.

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Physical Properties of Isolated Perfused Renal Tubular Basement Membranes

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100065997 ◽

1971 ◽

Vol 29 ◽

pp. 390-391

Author(s):

Jared Grantham ◽

Larry Welling

Keyword(s):

Basement Membrane ◽

Basement Membranes ◽

Transport Mechanisms ◽

Permeability Characteristics ◽

Peritubular Capillaries ◽

Strategic Location ◽

Tubular Lumen ◽

Glomerular Filtrate ◽

Urine Formation ◽

Renal Tubular

In the course of urine formation in mammalian kidneys over 90% of the glomerular filtrate moves from the tubular lumen into the peritubular capillaries by both active and passive transport mechanisms. In all of the morphologically distinct segments of the renal tubule, e.g. proximal tubule, loop of Henle and distal nephron, the tubular absorbate passes through a basement membrane which rests against the basilar surface of the epithelial cells. The basement membrane is in a strategic location to affect the geometry of the tubules and to influence the movement of tubular absorbate into the renal interstitium. In the present studies we have determined directly some of the mechanical and permeability characteristics of tubular basement membranes.

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