Role of arginine vasopressin in medullary thick ascending limb on maximal urinary concentration

1986 ◽  
Vol 251 (2) ◽  
pp. F266-F270 ◽  
Author(s):  
J. K. Kim ◽  
S. N. Summer ◽  
A. E. Erickson ◽  
R. W. Schrier
Keyword(s):  
Adenylate Cyclase ◽  
Arginine Vasopressin ◽  
Urinary Concentration ◽  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
Urinary Osmolality ◽  
Medullary Thick Ascending Limb ◽  
Sprague Dawley Rats ◽  
Collecting Tubules

Two groups of Sprague-Dawley rats, Harlan (H) and Charles River (CR), were discovered in that the medullary thick ascending limb (MAL) had a profoundly different adenylate cyclase response to arginine vasopressin (AVP). Using these two groups of rats, we studied the correlation between AVP action on the MAL and maximal urinary concentration. AVP (10(-6) M) significantly stimulated adenylate cyclase in MAL of H rats (7.4 +/- 0.9 to 43.8 +/- 4.6 fmol cAMP formed X 30 min-1 X mm-1, P less than 0.001) but not in CR rats (10.3 +/- 1.4 to 12.7 +/- 2.0 fmol cAMP formed X 30 min-1 X mm-1, NS). In contrast, AVP significantly stimulated adenylate cyclase of cortical, outer and inner medullary collecting tubules from both H and CR rats. Glucagon (10(-6) M) significantly stimulated adenylate cyclase of MAL from both H and CR rats. After 48 h of fluid deprivation, urinary osmolality was significantly higher (P less than 0.001) in the H (4,504 +/- 399 mosmol/kg H2O, n = 14) than CR (2,840 +/- 176 mosmol/kg H2O, n = rats. This observation was not attributable to differences in creatinine clearance (CR, 1.30 +/- 0.24; H, 1.24 +/- 0.03 ml/min, NS, n = 4) or plasma AVP (CR, 12.75 +/- 1.44; H, 12.38 +/- 1.17 pg/ml, NS, n = 6) levels. These results therefore suggest that the action of AVP on the MAL, in addition to the effect on collecting tubules, is involved in maximal urinary concentration in rats.

Cellular action of arginine vasopressin in the isolated renal tubules of hypothyroid rats

1987 ◽  
Vol 253 (1) ◽  
pp. F104-F110 ◽  
Author(s):  
J. K. Kim ◽  
S. N. Summer ◽  
R. W. Schrier
Keyword(s):  
Adenylate Cyclase ◽  
Arginine Vasopressin ◽  
Morphological Changes ◽  
Renal Tubules ◽  
Thick Ascending Limb ◽  
Urinary Volume ◽  
Outer Medulla ◽  
Urinary Osmolality ◽  
Medullary Thick Ascending Limb ◽  
Collecting Tubules

Hypothyroidism has been demonstrated to be associated with an impaired concentrating capacity and specific morphological changes in the thick ascending limbs. This study was performed to evaluate the cellular action of arginine vasopressin (AVP) in the isolated renal tubules from control (C) and hypothyroid (HT) rats. Hypothyroidism was induced by feeding aminotriazole for 4 wk. Urinary volume was higher in HT rats (C 13.5 +/- 0.9, HT 17.7 +/- 0.9 ml/24 h, P less than 0.005) and urinary osmolality was lower in HT rats (C 1,707 +/- 49, HT 1,229 +/- 35 mosmol/kgH2O, P less than 0.001). Plasma AVP levels were significantly higher in HT rats (C 1.93 +/- 0.59, HT 4.12 +2- 0.62 pg/ml, P less than 0.05), thus documenting AVP resistance. The adenylate cyclase response to AVP (10(-6) M) was significantly lower (P less than 0.02) in the medullary thick ascending limb of Henle's loop (mTALH) in HT (14.3 +/- 2.4 to 41.7 +/- 5.8 fm X 30 min-1 X mm-1, P less than 0.001) than in mTALH in C rats (14.4 +/- 2.8 to 110.1 +/- 24.9 fm X 30 min-1 X mm-1, P less than 0.001). In contrast, the adenylate cyclase response to AVP was not significantly different in collecting tubules of cortex, outer medulla, and inner medulla from C and HT rats, although a slight decrease in response to AVP was observed in cortical and outer medullary collecting tubules.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic intravenous administration of V1 arginine vasopressin agonist results in sustained hypertension

1994 ◽  
Vol 267 (2) ◽  
pp. H751-H756 ◽  
Author(s):  
A. W. Cowley ◽  
E. Szczepanska-Sadowska ◽  
K. Stepniakowski ◽  
D. Mattson
Keyword(s):  
Body Weight ◽  
Arginine Vasopressin ◽  
Plasma Catecholamines ◽  
Plasma Osmolality ◽  
Sprague Dawley ◽  
Prolonged Administration ◽  
Chronic Stimulation ◽  
Sustained Hypertension ◽  
Sprague Dawley Rats

Despite the well-recognized vasoconstrictor and fluid-retaining actions of vasopressin, prolonged administration of arginine vasopressin (AVP) to normal animals or humans fails to produce sustained hypertension. The present study was performed to elucidate the role of the V1 receptor in determining the ability of AVP to produce sustained hypertension. Conscious Sprague-Dawley rats with implanted catheters were infused with the selective V1 agonist, [Phe2,Ile3,Orn8]vasopressin (2 ng.kg-1.min-1), for 14 days in amounts that were acutely nonpressor. Blood pressure (MAP), heart rate (HR), body weight, and water intake (WI) were determined daily. Plasma AVP, plasma catecholamines norepinephrine and epinephrine, plasma osmolality, and electrolyte concentration were determined before and on days 1 and 7 of infusion. MAP increased significantly by 10.4 +/- 4.5 mmHg on day 1 and rose to 22 +/- 5 mmHg above control by day 14 (transient decrease on days 6-9) and then fell to control levels after the infusion was stopped. HR did not change significantly. Plasma AVP immunoreactivity increased from 2.5 +/- 0.3 to 10.9 +/- 2.1 pg/ml, whereas norepinephrine tended to fall only on day 1, with epinephrine only slightly elevated on day 7. No evidence of fluid retention was found, and rats lost sodium only on the first day of V1 agonist infusion. Body weight increased throughout the study but was unrelated to the changes of MAP. We conclude that chronic stimulation of V1 receptors results in sustained hypertension in rats.

Stimulation of Na+/K+-ATPase activity by polyamines in the rat renal medullary cells of the thick ascending limb of Henle's loop

1990 ◽  
Vol 127 (3) ◽  
pp. 377-382 ◽  
Author(s):  
J. A. Charlton ◽  
P. H. Baylis
Keyword(s):  
Atpase Activity ◽  
Arginine Vasopressin ◽  
Thick Ascending Limb ◽  
Stimulus Response ◽  
Spermine Synthase ◽  
Medullary Thick Ascending Limb ◽  
Henle's Loop ◽  
Specific Inhibitors ◽  
Stimulation Of

ABSTRACT Previous studies have indicated that ornithine decarboxylase (ODC) may be involved in the stimulation of Na+/K+-ATPase activity by arginine vasopressin (AVP) in the rat renal medullary thick ascending limb of Henle's loop. The present study was aimed at establishing the role of the polyamines, the conversion products of ODC activity, in the stimulation of Na+/K+-ATPase by AVP. Using cytochemical methods, we have demonstrated an increase in Na+/K+-ATPase activity after stimulation with putrescine, spermidine and spermine (each 1 mmol/l) for 2·5,2 and 1·5 min respectively. The specific inhibitors of spermidine and spermine synthase, bis-cyclohexylammonium sulphate and N-alkylated-1,3-diaminopropane respectively, inhibited the stimulation of Na+/K+-ATPase by AVP, this inhibition being reversed by spermine. These findings suggest that polyamines are involved in the stimulus-response coupling of the hormone-mediated response. Journal of Endocrinology (1990) 127, 377–382

scholarly journals Maleic acid-induced proximal tubulopathy: Na:K pump inhibition.

1993 ◽  
Vol 4 (2) ◽  
pp. 142-147
Author(s):  
S K Mujais
Keyword(s):  
Maleic Acid ◽  
Transport Processes ◽  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Pump Activity ◽  
Proximal Tubulopathy ◽  
The Many ◽  
Dependent Transport ◽  
Collecting Tubules

Maleic acid (MA) administration to experimental animals induces a rapid, reversible, complex dysfunction of the renal tubule resembling Fanconi's syndrome. The intent of this work was to characterize the changes in the Na:K pump along the nephron during the development and recovery from MA injury to better define the site of damage and to correlate the observed changes in Na:K pump function with alterations in metabolic function. Male Sprague Dawley rats were studied before and 2 and 24 h after the injection of MA (100 mg/kg iv). MA induced an early and reversible decline in Na:K pump activity in the proximal convoluted tubule (PCT) from 2,324 +/- 61 to 1,446 +/- 55 pmol/mm.h (P < 0.001). This decrement was transient because enzyme activity returned to near baseline by 24 h after MA administration. The changes in Na:K pump activity were restricted to the PCT because no change in pars rectae, in medullary thick ascending limb, or in medullary collecting tubules was observed. PCT obtained from MA-treated rats 2 h after drug injection showed a decline in 14CO2 formation from radiolabeled glutamine, implying impaired oxidation of the carbon skeleton of the amino acid. This decline was transient with recovery of oxidative rates to normal 24 h after MA administration. It was concluded that a reversible, segment-specific impairment in PCT Na:K pump occurs early after the administration of MA. The decline in PCT Na:K pump activity is paralleled by a decrement in oxidative metabolism and may underlie the many consequences of this model of proximal tubulopathy that are reflections of impairment in sodium-dependent transport processes.

scholarly journals Regulation of the renal Na:K pump: role of progesterone.

1993 ◽  
Vol 3 (8) ◽  
pp. 1488-1495
Author(s):  
S K Mujais ◽  
N A Nora ◽  
Y Chen
Keyword(s):  
Inhibitory Effect ◽  
Proximal Convoluted Tubule ◽  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
Medullary Thick Ascending Limb ◽  
Progesterone Treatment ◽  
Sprague Dawley Rats ◽  
High K ◽  
Pump Activity ◽  
Intact Rats

In male Sprague-Dawley rats, the effects of exogenous high physiologic levels of progesterone simulating those observed in pregnancy (5 mg/day) on Na:K pump activity (picomoles per millimeter per hour) in microdissected nephron segments were evaluated. In adrenal-intact rats, progesterone led to a generalized decrease in Na:K pump activity in proximal convoluted tubule from 2,524 +/- 61 to 741 +/- 41 (71% reduction; P < 0.01), medullary thick ascending limb (MAL) from 4,793 +/- 217 to 2,000 +/- 133 (59% reduction; P < 0.01), and cortical collecting tubule (CCT) from 1,141 +/- 69 to 591 +/- 133 (49% reduction; P < 0.01). This effect was similar in magnitude to the decline observed with adrenalectomy alone. In adrenalectomized rats, progesterone had no further inhibitory effect on the pump in MAL (2,172 +/- 66 versus 2,312 +/- 71) or CCT (493 +/- 58 versus 530 +/- 31) but led to a modest decline in Na:K pump activity in the proximal convoluted tubule (from 1,136 +/- 88 to 528 +/- 31; P < 0.01). In adrenal-intact rats, a high K diet for 7 days led to an increase in CCT Na:K pump activity from 1,141 +/- 69 on a normal potassium diet to 2,224 +/- 33 pmol/mm per h (P < 0.001). Progesterone treatment reduced basal Na:K pump activity in CCT, and concurrent progesterone treatment blunted the stimulatory effect of K adaptation on the pump (973 +/- 68 pmol/mm per h; P < 0.001 versus untreated).(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced expression of renal Na+ transporters in rats with PTH-induced hypercalcemia

2004 ◽  
Vol 286 (3) ◽  
pp. F534-F545 ◽  
Author(s):  
Weidong Wang ◽  
Chunling Li ◽  
Tae-Hwan Kwon ◽  
R. Tyler Miller ◽  
Mark A. Knepper ◽  
...  
Keyword(s):  
Fractional Excretion ◽  
Urinary Concentration ◽  
High Dose ◽  
Thick Ascending Limb ◽  
Urinary Osmolality ◽  
Protein Levels ◽  
Severe Hypercalcemia ◽  
Type 3

The purpose of this study was to evaluate whether the natriuresis and polyuria seen in parathyroid hormone (PTH)-induced hypercalcemia are associated with dysregulation of renal Na transporters. Rats were infused with three different doses of human PTH [PTH ( 1 - 34 ); 7.5, 10, and 15 μg·kg-1·day-1 sc] or vehicle for 48 h using osmotic minipumps. The rats treated with PTH developed significant hypercalcemia (plasma total calcium levels: 2.71 ± 0.03, 2.77 ± 0.02, and 3.42 ± 0.06 mmol/l, respectively, P < 0.05 compared with corresponding controls). The rats with severe hypercalcemia induced by high-dose PTH developed a decreased glomerular filtration rate (GFR), increased urine output, reduced urinary osmolality, increased urinary Na excretion, and fractional excretion of Na. This was associated with downregulation (calculated as a fraction of control levels) of whole kidney expression of type 2 Na-Pi cotransporter (NaPi-2; 16 ± 6%), type 3 Na/H exchanger (NHE3; 42 ± 7%), Na-K-ATPase (55 ± 2%), and bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1; 25 ± 4%). In contrast, an upregulation of the Ca2+-sensing receptor (CaR) was observed. Rats treated with moderate-dose PTH exhibited unchanged GFR but decreased urinary concentration. The whole kidney expression of NHE3 (52 ± 8%) and NaPi-2 (26 ± 5%) was persistently decreased, whereas BSC-1 and Na-K-ATPase protein levels were not altered. CaR expression was also increased. Moreover, rats treated with low-dose PTH showed very mild hypercalcemia but unchanged GFR, normal urinary concentration, and unchanged expression of Na transporters and CaR. In conclusion, the reduced expression of major renal Na transporters is likely to play a role in the increased urinary Na excretion and decreased urinary concentration in rats with PTH-induced hypercalcemia. Moreover, the increase in the CaR in the thick ascending limb (TAL) may indicate a potential role of the CaR in inhibiting Na transport in the TAL.

scholarly journals Treating lithium-induced nephrogenic diabetes insipidus with a COX-2 inhibitor improves polyuria via upregulation of AQP2 and NKCC2

2008 ◽  
Vol 294 (4) ◽  
pp. F702-F709 ◽  
Author(s):  
Gheun-Ho Kim ◽  
Nak Won Choi ◽  
Ju-Young Jung ◽  
Ji-Hyun Song ◽  
Chang Hwa Lee ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Collecting Duct ◽  
Urine Osmolality ◽  
Urinary Concentration ◽  
Prostaglandin E ◽  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Cox 2

Prostaglandin E2 may antagonize vasopressin-stimulated salt absorption in the thick ascending limb and water absorption in the collecting duct. Blockade of prostaglandin E2 synthesis by nonsteroidal anti-inflammatory drugs (NSAIDs) enhances urinary concentration, and these agents have antidiuretic effects in patients with nephrogenic diabetes insipidus (NDI) of different etiologies. Because renal prostaglandins are derived largely from cyclooxygenase-2 (COX-2), we hypothesized that treatment of NDI with a COX-2 inhibitor may relieve polyuria through increased expression of Na-K-2Cl cotransporter type 2 (NKCC2) in the thick ascending limb and aquaporin-2 (AQP2) in the collecting duct. To test this hypothesis, semiquantitative immunoblotting and immunohistochemistry were carried out from the kidneys of lithium-induced NDI rats with and without COX-2 inhibition. After male Sprague-Dawley rats were fed an LiCl-containing rat diet for 3 wk, the rats were randomly divided into control and experimental groups. The COX-2 inhibitor DFU (40 mg·kg−1·day−1) was orally administered to the experimental rats for an additional week. Treatment with the COX-2 inhibitor significantly relieved polyuria and raised urine osmolality. Semiquantitative immunoblotting using whole-kidney homogenates revealed that COX-2 inhibition caused significant increases in the abundance of AQP2 and NKCC2. Immunohistochemistry for AQP2 and NKCC2 confirmed the effects of COX-2 inhibition in lithium-induced NDI rats. The upregulation of AQP2 and NKCC2 in response to the COX-2 inhibitor may underlie the therapeutic mechanisms by which NSAIDs enhance antidiuresis in patients with NDI.

Role of hemodynamic factors in osmoregulatory alterations of rat pregnancy

1989 ◽  
Vol 257 (4) ◽  
pp. R909-R916
Author(s):  
W. M. Barron ◽  
J. A. Durr ◽  
R. W. Schrier ◽  
M. D. Lindheimer
Keyword(s):  
Blood Pressure ◽  
Arginine Vasopressin ◽  
Volume Expansion ◽  
Plasma Osmolality ◽  
Effective Volume ◽  
Sprague Dawley ◽  
Deoxycorticosterone Acetate ◽  
Sprague Dawley Rats ◽  
In Pregnancy

Plasma osmolality (Posmol) decreases in pregnancy, possibly because of hemodynamically mediated arginine vasopressin (AVP) secretion, i.e., inadequate vascular filling and/or decreased blood pressure. This hypothesis was tested in Sprague-Dawley rats treated on gestational days 1-18 or 13-18 with 1) deoxycorticosterone acetate (DOCA) + standard chow (0.5% Na), 2) vehicle + standard chow, or 3) high-Na (1.25%) diet. Renal sodium "escape" and suppression of the renin-aldosterone system suggested "effective volume expansion," yet Posmol was similar in all pregnant groups, 7-10 mosmol/kg below levels in virgin controls, and plasma AVP was unaltered. Apparent osmotic thresholds for AVP secretion, similar in control and DOCA-treated gravid animals, were 8-10 mosmol/kg below those of untreated virgin rats. Norepinephrine + DOCA, administered to gravid animals consuming normal or high-Na chow, increased blood pressure approximately 10% above control levels, but this also failed to alter Posmol. These data suggest that mechanisms other than hemodynamically mediated AVP secretion are responsible for the osmoregulatory alterations accompanying rodent pregnancy.

scholarly journals Mild DOCA-salt hypertension: sympathetic system and role of renal nerves

2011 ◽  
Vol 300 (5) ◽  
pp. H1781-H1787 ◽  
Author(s):  
Sachin S. Kandlikar ◽  
Gregory D. Fink
Keyword(s):  
Control Period ◽  
Whole Body ◽  
Renal Nerves ◽  
Experimental Hypertension ◽  
Sympathetic Activation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Salt Hypertension ◽  
Hypertension Development

Excess sympathetic nervous system activity (SNA) is linked to human essential and experimental hypertension. To test whether sympathetic activation is associated with a model of deoxycorticosterone acetate (DOCA)-salt hypertension featuring two kidneys and a moderate elevation of blood pressure, we measured whole body norepinephrine (NE) spillover as an index of global SNA. Studies were conducted in chronically catheterized male Sprague-Dawley rats drinking water containing 1% NaCl and 0.2% KCl. After a 7-day surgical recovery and a 3-day control period, a DOCA pellet (50 mg/kg) was implanted subcutaneously in one group of rats (DOCA), while the other group underwent sham implantation (Sham). NE spillover was measured on control day 2 and days 7 and 14 after DOCA administration or sham implantation. During the control period, mean arterial pressure (MAP) was similar in Sham and DOCA rats. MAP was significantly increased in the DOCA group compared with the Sham group after DOCA administration ( day 14: Sham = 109 ± 5.3, DOCA = 128 ± 3.6 mmHg). However, plasma NE concentration, clearance, and spillover were not different in the two groups at any time. To determine whether selective sympathetic activation to the kidneys contributes to hypertension development, additional studies were performed in renal denervated (RDX) and sham-denervated (Sham-DX) rats. MAP, measured by radiotelemetry, was similar in both groups during the control and DOCA treatment periods. In conclusion, global SNA is not increased during the development of mild DOCA-salt hypertension, and fully intact renal nerves are not essential for hypertension development in this model.

Sign in / Sign up

Export Citation Format

Share Document