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Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation.
Niimura F, Labosky PA, Kakuchi J, Okubo S, Yoshida H, Oikawa T, Ichiki T, Naftilan AJ, Fogo A, Inagami T
(1995) J Clin Invest 96: 2947-54
MeSH Terms: Aging, Angiotensin II, Angiotensinogen, Animals, Blood Pressure, Body Weight, Gene Expression, Growth Substances, Homeostasis, Kidney, Kidney Cortex, Kidney Glomerulus, Kidney Medulla, Mice, Mice, Knockout, Mice, Mutant Strains, Organ Size, Platelet-Derived Growth Factor, RNA, Messenger, Restriction Mapping, Transforming Growth Factor beta
Show Abstract · Added January 20, 2012
Elevated levels of endogenous angiotensin can cause hypertensive nephrosclerosis as a result of the potent vasopressor action of the peptide. We have produced by gene targeting mice homozygous for a null mutation in the angiotensinogen gene (Atg-1-). Postnatally, Atg-1- animals show a modest delay in glomerular maturation. Although Atg-1- animals are hypotensive by 7 wk of age, they develop, by 3 wk of age, pronounced lesions in the renal cortex, similar to those of hypertensive nephrosclerosis. In addition, the papillae of homozygous mutant kidneys are reduced in size. These lesions are accompanied by local up-regulation of PDGF-B and TGF-beta1 mRNA in the cortex and down-regulation of PDGF-A mRNA in the papilla. The study demonstrates an important requirement for angiotensin in achieving and maintaining the normal morphology of the kidney. The mechanism through which angiotensin maintains the volume homeostasis in mammals includes promotion of the maturational growth of the papilla.
2 Communities
2 Members
0 Resources
21 MeSH Terms
ddAVP does not stimulate acute changes in levels of medullary trimethylamines in humans.
Avison MJ, Van Why SK, Siegel NJ
(1993) J Am Soc Nephrol 4: 1379-84
MeSH Terms: Adult, Deamino Arginine Vasopressin, Humans, Injections, Intravenous, Kidney Medulla, Magnetic Resonance Spectroscopy, Methylamines, Osmolar Concentration, Urine, Water-Electrolyte Balance
Show Abstract · Added December 10, 2013
1H nuclear magnetic resonance has been used to determine the effect of acute iv administration of the arginine vasopressin analog 1-(3-mercaptopropionic acid)-8-D-arginine vasopressin monoacetate (ddAVP; 2 micrograms) on renal medullary trimethylamine (TMA) levels in human volunteers. In subjects deprived of food and water for 15 h, urine osmolality (Uosm) was 889 +/- 47 mosmol/kg and had not changed significantly 3 h after ddAVP administration. Medullary TMA did not change significantly over 3 h after ddAVP. In a second group of subjects who were well hydrated, acute ddAVP infusion increased Uosm from 203 +/- 63 to 421 +/- 47 mosmol/kg in 3 h (P < 0.05). However, medullary TMA did not change significantly over this time period. These results indicate that ddAVP, and presumably arginine vasopressin, do not acutely influence medullary TMA levels, and they support the view that results previously reported for animal and isolated cell systems are also applicable to human physiology.
0 Communities
1 Members
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10 MeSH Terms
Response of rat inner medullary collecting duct to epidermal growth factor.
Harris RC
(1989) Am J Physiol 256: F1117-24
MeSH Terms: Animals, Arachidonic Acids, Cells, Cultured, Cyclic AMP, DNA Replication, Dinoprostone, Epidermal Growth Factor, ErbB Receptors, Kidney Medulla, Kidney Tubules, Kidney Tubules, Collecting, Kinetics, Male, Rats, Rats, Inbred Strains, Tetradecanoylphorbol Acetate
Show Abstract · Added January 28, 2014
Urine is an abundant source of epidermal growth factor (EGF) and prepro-EGF has been localized to the thick ascending limb and distal convoluted tubule of the kidney. However, the functional role of EGF in the kidney is poorly understood. Determination of EGF receptors and functional responses to EGF in intrarenal structures distal to the site of renal EGF production may prove critical to our understanding of the role of this peptide. These studies were designed to investigate the response to EGF of rat inner medullary collecting duct cells in culture and in freshly isolated suspensions. Primary cultures of inner medullary collecting duct cells demonstrated equilibrium binding of 125I-labeled EGF at 4 and 23 degrees C. At 23 degrees C, there was 89 +/- 1% specific binding (n = 30). Scatchard analysis of 125I-EGF binding suggested the presence of both high-affinity binding with a dissociation constant (Kd) of 5 X 10(-10) M and maximal binding sites (Ro) of 2.7 X 10(3) binding sites/cell and low-affinity binding, with Kd of 8.3 X 10(-9) M and Ro of 1.8 X 10(4) binding sites/cell. Bound EGF, 68 +/- 3%, was internalized by 45 min. EGF binding was not inhibited by antidiuretic hormone, atrial natriuretic peptide or bradykinin at 23 degrees C, but there was concentration-dependent inhibition of binding by transforming growth factor-alpha. Incubation with phorbol myristate acetate decreased 125I-EGF binding in a concentration-dependent manner. 125I-EGF binding was also demonstrated in freshly isolated suspensions of rat inner medullary collecting duct cells.(ABSTRACT TRUNCATED AT 250 WORDS)
1 Communities
1 Members
0 Resources
16 MeSH Terms
1H NMR study of renal trimethylamine responses to dehydration and acute volume loading in man.
Avison MJ, Rothman DL, Nixon TW, Long WS, Siegel NJ
(1991) Proc Natl Acad Sci U S A 88: 6053-7
MeSH Terms: Adult, Dehydration, Drinking, Humans, Hydrogen, Kidney, Kidney Medulla, Magnetic Resonance Spectroscopy, Male, Methylamines, Water
Show Abstract · Added December 10, 2013
We have used volume-localized 1H NMR spectroscopy to detect and measure changes in medullary trimethylamines (TMAs) in the human kidney in vivo. Localized water-suppressed 1H spectra were collected from a volume of interest located within the renal medulla by using a stimulated echo-based localization scheme. The principal resonances in the medullary 1H spectrum were residual water (4.7 ppm), lipid (0.9-1.4 ppm), and TMAs (3.25 ppm). The TMA line width was 7-15 Hz before filtering, and the signal-to-noise ratio was 40:1. In four normal volunteers, 15 hr of dehydration led to a significant increase in urine osmolality and decrease in body weight and an increase in medullary TMAs. A subsequent water load [20 ml.(kg of body weight)-1] caused a transient water diuresis, a return to euvolemic body weight, and a significant reduction in medullary TMAs within 4 hr. These results suggest that TMAs may play an osmoregulatory role in the medulla of the normal human kidney.
0 Communities
1 Members
0 Resources
11 MeSH Terms
Intracellular granules of the renal medulla in a case of potassium depletion due to renal potassium wasting. Electron microscopic comparison with renal medullary granules in the potassium-depleted rat.
France R, Gray ME, Stone WJ, Swift LL
(1978) Am J Pathol 91: 299-312
MeSH Terms: Animals, Cytoplasmic Granules, Female, Glycoproteins, Humans, Hypokalemia, Kidney, Kidney Cortex, Kidney Diseases, Kidney Medulla, Male, Middle Aged, Periodic Acid-Schiff Reaction, Potassium Deficiency, Rats
Show Abstract · Added May 27, 2014
An electron microscopic comparison was made of intracellular granules of the renal papilla and inner medulla in two types of potassium depletion: one in a 47-year-old white male with chronic potassium-wasting renal disease and the other in the experimentally depleted rat. The granules in both cases were composed of small and large vesicles; myelin figures; small particles; and dense bodies, with a partial, or complete, single limiting membrane. Ultrastructurally, the constituent elements of the granules were essentially the same in the two types of potassium depletion. It was concluded that the intracellular granules in the human tissue were the result of potassium depletion and a counterpart to those in the potassium-depleted rat.
0 Communities
1 Members
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15 MeSH Terms
Ionophores stimulate prostaglandin and thromboxane biosynthesis.
Knapp HR, Oelz O, Roberts LJ, Sweetman BJ, Oates JA, Reed PW
(1977) Proc Natl Acad Sci U S A 74: 4251-5
MeSH Terms: Arachidonic Acids, Blood Platelets, Humans, In Vitro Techniques, Ionophores, Kidney Medulla, Male, Prostaglandins, Stimulation, Chemical, Thromboxane B2, Thromboxanes, Time Factors
Show Abstract · Added December 10, 2013
The role of calcium in triggering prostaglandin and thromboxane synthesis was studied in several systems with ionophores of different ion specificities. Divalent cationophore A23187 stimulates prostaglandin and thromboxane production by washed human platelets in a concentration-dependent manner (0.3-9 muM). A23187 also induces an antimycin A-insensitive burst in oxygen utilization which is partially blocked by 5 mM aspirin or 10 muM indomethacin. Under our conditions, A23187 (up to 10 muM) does not appear to damage platelet membranes since it does not cause appreciable loss of lactate dehydrogenase or beta-glucuronidase. Mono- and divalent cationophore X537A also stimulates platelet thromboxane B(2) production and oxygen utilization, but monovalent cationophores nigericin, monensin A, A204, and valinomycin have no effect. The synthesis of prostaglandins E(2), D(2), and F(2alpha) by rat renal medulla mince is stimulated by 1 and 5 muM A23187 without changes in tissue ATP content, lactate output, or K(+) efflux. X537A, monensin A, and nigericin (all 5 muM) stimulate both prostaglandin output and K(+) efflux from renal medulla, while 5 muM valinomycin or A204 has no effect on either. None of the ionophores stimulates renomedullary prostaglandin production if calcium is omitted from the incubation medium. A23187 also stimulates prostaglandin production by human lymphoma cells, rat stomach and trachea preparations, and guinea pig polymorphonuclear leukocytes. These observations suggest a major role for Ca(2+) in stimulating prostaglandin and thromboxane biosynthesis, and also indicate that prostaglandin and/or thromboxane release may partially mediate some of the previously described effects of ionophores on cells and tissues.
0 Communities
1 Members
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12 MeSH Terms