scholarly journals AT1a receptor signaling is required for basal and water deprivation-induced urine concentration in AT1a receptor-deficient mice

2012 ◽  
Vol 303 (5) ◽  
pp. F746-F756 ◽  
Author(s):  
Xiao C. Li ◽  
Yuan Shao ◽  
Jia L. Zhuo
Keyword(s):  
Adenylyl Cyclase ◽  
Water Deprivation ◽  
Urine Osmolality ◽  
Urine Concentration ◽  
Ang Ii ◽  
Receptor Signaling ◽  
Urine Excretion ◽  
Lower Systolic Blood Pressure ◽  
At1a Receptor ◽  
Total Lysate

It is well recognized that ANG II interacts with arginine vasopressin (AVP) to regulate water reabsorption and urine concentration in the kidney. The present study used ANG II type 1a (AT1a) receptor-deficient (Agtr1a−/−) mice to test the hypothesis that AT1a receptor signaling is required for basal and water deprivation-induced urine concentration in the renal medulla. Eight groups of wild-type (WT) and Agtr1a−/− mice were treated with or without 24-h water deprivation and 1-desamino-8-d-AVP (DDAVP; 100 ng/h ip) for 2 wk or with losartan (10 mg/kg ip) during water deprivation. Under basal conditions, Agtr1a−/− mice had lower systolic blood pressure ( P < 0.01), greater than threefold higher 24-h urine excretion (WT mice: 1.3 ± 0.1 ml vs. Agtr1a−/− mice: 5.9 ± 0.7 ml, P < 0.01), and markedly decreased urine osmolality (WT mice: 1,834 ± 86 mosM/kg vs. Agtr1a−/− mice: 843 ± 170 mosM/kg, P < 0.01), without significant changes in 24-h urinary Na+ excretion. These responses in Agtr1a−/− mice were associated with lower basal plasma AVP (WT mice: 105 ± 8 pg/ml vs. Agtr1a−/− mice: 67 ± 6 pg/ml, P < 0.01) and decreases in total lysate and membrane aquaporin-2 (AQP2; 48.6 ± 7% of WT mice, P < 0.001) and adenylyl cyclase isoform III (55.6 ± 8% of WT mice, P < 0.01) proteins. Although 24-h water deprivation increased plasma AVP to the same levels in both strains, 24-h urine excretion was still higher, whereas urine osmolality remained lower, in Agtr1a−/− mice ( P < 0.01). Water deprivation increased total lysate AQP2 proteins in the inner medulla but had no effect on adenylyl cyclase III, phosphorylated MAPK ERK1/2, and membrane AQP2 proteins in Agtr1a−/− mice. Furthermore, infusion of DDAVP for 2 wk was unable to correct the urine-concentrating defects in Agtr1a−/− mice. These results demonstrate that AT1a receptor-mediated ANG II signaling is required to maintain tonic AVP release and regulate V2 receptor-mediated responses to water deprivation in the inner medulla.

Normal Urine Concentrating Ability in Magnesium Depletion

1972 ◽  
Vol 43 (6) ◽  
pp. 723-729 ◽  
Author(s):  
S. M. Suh ◽  
J. Sellors
Keyword(s):  
Water Deprivation ◽  
Urine Osmolality ◽  
Urine Concentration ◽  
Potassium Depletion ◽  
Magnesium Depletion ◽  
Normal Urine ◽  
Urine Concentrating Ability

1. We studied urine concentrating ability in ten magnesium-depleted puppies and compared the results with those of match-fed, littermate controls. 2. The experimental puppies became hypomagnesaemic and hypocalcaemic without evidence of potassium depletion. After 24 h of food and water deprivation, urine osmolality increased to 1350 ± 340 mosm/kg of water. This value did not differ from that of control animals. 3. We also studied urine concentrating ability in a child with primary hypomagnesaemia and secondary hypocalcaemia. He could achieve a urine concentration of 1080 mosm/kg of water after 20 h of water deprivation when he was hypomagnesaemic and hypocalcaemic. 4. We conclude that urine concentrating ability is normal in magnesium depletion uncomplicated by hypercalcaemia or severe potassium depletion.

scholarly journals Collecting duct-specific knockout of adenylyl cyclase type VI causes a urinary concentration defect in mice

2012 ◽  
Vol 302 (1) ◽  
pp. F78-F84 ◽  
Author(s):  
Karl P. Roos ◽  
Kevin A. Strait ◽  
Kalani L. Raphael ◽  
Mitsi A. Blount ◽  
Donald E. Kohan
Keyword(s):  
Adenylyl Cyclase ◽  
Water Intake ◽  
Arginine Vasopressin ◽  
Water Deprivation ◽  
Collecting Duct ◽  
Urine Volume ◽  
Urine Osmolality ◽  
Camp Accumulation ◽  
Water Excretion ◽  
Normal Water

Collecting duct (CD) adenylyl cyclase VI (AC6) has been implicated in arginine vasopressin (AVP)-stimulated renal water reabsorption. To evaluate the role of CD-derived AC6 in regulating water homeostasis, mice were generated with CD-specific knockout (KO) of AC6 using the Cre/loxP system. CD AC6 KO and controls were studied under normal water intake, chronically water loaded, or water deprived; all of these conditions were repeated in the presence of continuous administration of 1-desamino-8-d-arginine vasopressin (DDAVP). During normal water intake or after water deprivation, urine osmolality (Uosm) was reduced in CD AC6 KO animals vs. controls. Similarly, Uosm was decreased in CD AC6 KO mice vs. controls after water deprivation+DDAVP administration. Pair-fed (with controls) CD AC6 KO mice also had lower urine osmolality vs. controls. There were no detectable differences between KO and control animals in fluid intake or urine volume under any conditions. CD AC6 KO mice did not have altered plasma AVP levels vs. controls. AVP-stimulated cAMP accumulation was reduced in acutely isolated inner medullary CD (IMCD) from CD A6 KO vs. controls. Medullary aquaporin-2 (AQP2) protein expression was lower in CD AC6 KO mice vs. controls. There were no differences in urinary urea excretion or IMCD UT-A1 expression; however, IMCD UT-A3 expression was reduced in CD AC6 KO mice vs. controls. In summary, AC6 in the CD regulates renal water excretion, most likely through control of AVP-stimulated cAMP accumulation and AQP2.

Abnormal water metabolism in mice lacking the type 1A receptor for ANG II

2000 ◽  
Vol 278 (1) ◽  
pp. F75-F82 ◽  
Author(s):  
Michael I. Oliverio ◽  
Marielle Delnomdedieu ◽  
Christopher F. Best ◽  
Ping Li ◽  
Mariana Morris ◽  
...  
Keyword(s):  
Water Deprivation ◽  
Critical Role ◽  
Urine Concentration ◽  
Urinary Concentration ◽  
Structural Abnormality ◽  
Ang Ii ◽  
Wild Type ◽  
Water Metabolism ◽  
Water Excretion ◽  
Plasma Vasopressin

Mice lacking AT1Areceptors for ANG II have a defect in urinary concentration manifested by an inability to increase urinary osmolality to levels seen in controls after thirsting. This defect results in extreme serum hypertonicity during water deprivation. In the basal state, plasma vasopressin levels are similar in wild-type controls and Agtr1a −/− mice. Plasma vasopressin levels increase normally in the AT1A receptor-deficient mice after 24 h of water deprivation, suggesting that the defect in urine concentration is intrinsic to the kidney. Using magnetic resonance microscopy, we find that the absence of AT1A receptors is associated with a modest reduction in the distance from the kidney surface to the tip of the papilla. However, this structural abnormality seems to play little role in the urinary concentrating defect in Agtr1a −/− mice since the impairment is largely reproduced in wild-type mice by treatment with an AT1-receptor antagonist. These studies demonstrate a critical role for the AT1A receptor in maintaining inner medullary structures in the kidney and in regulating renal water excretion.

THE USE OF CHLORPROPAMIDE IN DIABETES INSIPIDUS IN CHILDREN

PEDIATRICS ◽  
1970 ◽  
Vol 45 (2) ◽  
pp. 236-245
Author(s):  
Robert M. Ehrlich ◽  
Sang Whay Kooh
Keyword(s):  
Diabetes Insipidus ◽  
Water Deprivation ◽  
Plasma Insulin ◽  
Urine Volume ◽  
Insulin Response ◽  
Urine Osmolality ◽  
Post Traumatic ◽  
Term Management ◽  
Plasma Insulin Response

Oral chlorpropamide was administered to 17 children with diabetes insipidus (D.I.). The cause of the D.I. was idiopathic, six; histiocytosis, five; craniopharyngioma, three; pinealoma, two, and post-traumatic, one. Twenty-four-hour urine volume and measurements of serum and urine osmolality at the beginning and end of a 7-hour water deprivation test were used to evaluatechlorpropamide therapy. Administration of 150 to 400 mg of chlorpropamide per day by mouth caused a reduction in urine volume in all patients (range 8 to 67%). No change in aldosterone, 17-hydroxycorticoids, or electrolyte excretion was noted. Serum electrolytes and glomerular filtration rate were not affected by therapy. Glucose tolerance and plasma insulin response remained normal in those patients tested. Mild leucine sensitivity without significant change in plasma insulin was induced in four children. During water deprivation, seven patients with secondary D.I. but only one with idiopathic D.I. produced hypertonic urine. Hypoglycemia developed in seven children and is the major hazard of treatment. Long-term management of D.I. has been possible in nine children. Oral chlorpropamide is a useful drug in children with vasopressin-sensitive diabetes insipidus.

Cerebral metabolic responses and vasopressin and oxytocin secretions during progressive water deprivation in rats

1992 ◽  
Vol 262 (2) ◽  
pp. R310-R317 ◽  
Author(s):  
M. Kadekaro ◽  
J. Y. Summy-Long ◽  
S. Freeman ◽  
J. S. Harris ◽  
M. L. Terrell ◽  
...  
Keyword(s):  
Water Deprivation ◽  
Glucose Utilization ◽  
Extracellular Volume ◽  
Plasma Osmolality ◽  
Ventrolateral Medulla ◽  
Ang Ii ◽  
Neural Lobe ◽  
Arterial Blood ◽  
Organum Vasculosum Laminae Terminalis ◽  
Enhanced Secretion

Progressive water deprivation increased plasma osmolality, plasma Na+ concentration, and hematocrit in proportion to the severity of dehydration. With increases of 2% in plasma osmolality (24 h dehydration), glucose utilization increased in the supraoptic nuclei and tended to increase in the neural lobe. With further dehydration, glucose utilization also increased in the paraventricular nuclei. These increases were paralleled by depletion of vasopressin and oxytocin contents in the neural lobe and by the enhanced secretion of both hormones into plasma, with a predominant increase of vasopressin. These changes were proportional to the degree of dehydration. With progression of dehydration, decreases in intracellular and extracellular volumes accentuate. Reductions in extracellular volume result in increased angiotensin II (ANG II) formation. Accordingly, glucose utilization in the subfornical organ (SFO), a primary site of ANG II action, increased after 48 and 72 h of dehydration. The median preoptic nucleus, which receives direct inputs from the SFO, also increased glucose utilization at these times. Glucose utilization also increased in the organum vasculosum laminae terminalis, probably in response to the converging inputs from osmoreceptors, volume receptors, and ANG II receptors. Decreases in glucose utilization were observed in the caudal and rostral ventrolateral medulla, perhaps as compensatory responses to decreased extracellular volume to prevent fall in arterial blood pressure.

scholarly journals A noninternalized nondesensitized truncated AT1A receptor transduces an amplified ANG II signal

1998 ◽  
Vol 274 (2) ◽  
pp. E336-E345 ◽  
Author(s):  
Sophie Conchon ◽  
Nicolas Peltier ◽  
Pierre Corvol ◽  
Eric Clauser
Keyword(s):  
Inositol Phosphate ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Physiological Effect ◽  
Receptor Internalization ◽  
Ang Ii ◽  
Structural Determinants ◽  
Ovary Cells ◽  
Receptor Mutant ◽  
At1a Receptor

The structural determinants of the rat angiotensin (ANG) II AT1A receptor involved in receptor internalization, desensitization, and activation are investigated by producing six mutants that had progessively larger deletions of the cytoplasmic tail (−13, −19, −24, −31, −46, and −56 residues, respectively). After stable transfection of the cDNAs into Chinese hamster ovary cells, all mutants, except the most truncated, exhibit normal [Sar1]ANG II affinities [dissociation constant ( K d) = 0.19–0.70 nM] compared with the wild-type (WT) receptor ( K d = 0.62 nM) and are able to activate a Gq/11protein and a phospholipase C as measured by the ANG II-induced inositol phosphate (IP) turnover in the different clones. However, one of these mutants, Δ329 (deletion of 31 residues), exhibits a peculiar phenotype. This mutant shows a reduced ligand-induced internalization as measured by the acid-washing procedure (only 32% of receptors are internalized vs. 83% for WT). Moreover, the Δ329 mutant is less desensitized by a pretreatment with either ANG II (15% desensitization of ANG II-stimulated IP turnover vs. 60% for WT receptor) or the phorbol ester phorbol 12-myristate 13-acetate (no desensitization vs. 29% for WT receptor). These functional modifications of the Δ329 mutant are associated with the transduction of an amplified signal as demonstrated on both IP turnover and an integrated physiological effect of ANG II. Taken together, these data indicate that the sequence329SLSTKMS335of the rat AT1A receptor is involved in both receptor internalization and desensitization. This is the first demonstration that a desensitization- and internalization-defective AT1Areceptor mutant is also hyperreactive and mediates augmented cellular responses.

Water deprivation upregulates ANG II AT1 binding and mRNA in rat subfornical organ and anterior pituitary

1997 ◽  
Vol 273 (1) ◽  
pp. E156-E163 ◽  
Author(s):  
G. L. Sanvitto ◽  
O. Johren ◽  
W. Hauser ◽  
J. M. Saavedra
Keyword(s):  
Paraventricular Nucleus ◽  
Median Eminence ◽  
Anterior Pituitary ◽  
Water Deprivation ◽  
Subfornical Organ ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Ang Ii ◽  
At1 Receptors ◽  
Receptor Mrna

We studied angiotensin II (ANG II) receptor subtype expression in selected brain nuclei and pituitary gland after water deprivation by in vitro receptor autoradiography using 125I-labeled [Sar1]ANG II and by in situ hybridization using 35S-labeled AT1A, AT1B, and AT2 receptor-specific riboprobes. In control rats we found binding to AT1 receptors in the subfornical organ, paraventricular nucleus, median eminence, and anterior pituitary; AT1A mRNA expression in the subfornical organ and paraventricular nucleus; and AT1B mRNA expression in the anterior pituitary. No receptor mRNA was found in the median eminence. AT1 receptors and AT1A receptor mRNA levels were increased in the subfornical organ, and, in the anterior pituitary, AT1 receptors and AT1B receptor mRNA were increased, only after 5 days of water deprivation. No significant changes occurred after 1 or 3 days of water deprivation, and no regulation of ANG II receptor expression was detected in other brain areas. Our results show that prolonged water deprivation selectively regulates AT1 receptor expression and AT1A and AT1B receptor mRNA levels in the subfornical organ and anterior pituitary, respectively, supporting a role for these receptors during sustained dehydration.

Meclofenamate and urine concentration with and without exposure of the renal papilla

1981 ◽  
Vol 240 (5) ◽  
pp. F423-F429 ◽  
Author(s):  
R. J. Roman ◽  
C. Lechene
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Urine Osmolality ◽  
Urine Concentration ◽  
Prostaglandin Synthesis ◽  
Urine Flow ◽  
Renal Papilla ◽  
Arterial Blood ◽  
Pelvic Urine

The recent finding that inhibitors of prostaglandin synthesis prevent the fall in urine concentration produced by papillary exposure challenges the hypothesis that contact between the pelvic urine and papilla is essential to the renal concentrating process. The present study examines the change in urine osmolality produced by exposure of the renal papilla in rats given meclofenamate. In control animals urine osmolality(Uosmol) decreased 57% after 2 h of exposure of the renal papilla. In rats given meclofenamate 4 mg/kg urine osmolality increased 16%, urine flow decreased 30%, and glomerular filtration rate was unchanged in the nonexposed kidney. Meclofenamate, however, did not alter the decrease in Uosmol seen in the kidney with the exposed papilla. Meclofenamate 10 mg/kg was also ineffective in preventing the fall in urine osmolality produced by papillary exposure, although this higher dose decreased glomerular filtration rate and arterial blood pressure. These results are consistent with the finding that pelvic urine urea is important to the urinary concentrating process and with the hypothesis that urine osmolality falls after papillary exposure because contact between pelvic urine and papilla is interrupted.

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