Water retention after oral chlorpropamide is associated with an increase in renal papillary arginine vasopressin receptors

1995 ◽  
Vol 132 (4) ◽  
pp. 459-464 ◽  
Author(s):  
J Hensen ◽  
M Haenelt ◽  
P Gross
Keyword(s):  
Arginine Vasopressin ◽  
Water Retention ◽  
Specific Activity ◽  
High Specific Activity ◽  
Plasma Osmolality ◽  
Dependent Diabetes Mellitus ◽  
Scatchard Analysis ◽  
Sprague Dawley ◽  
Water Excretion ◽  
Vasopressin Receptors

Hensen J, Haenelt M, Gross P. Water retention after oral chlorpropamide is associated with an increase in renal papillary arginine vasopressin receptors. Eur J Endocrinol 1995;132:459–64. ISSN 0804–4643 Chlorpropamide (CP), a sulfonylurea used for treatment of non-insulin dependent diabetes mellitus, is known to potentiate the antidiuretic action of arginine vasopressin (AVP), predisposing to hyponatremia. It has been suggested that CP acts directly on the antidiuretic vasopressin receptor. Detailed studies on the influence of CP on the AVP receptor, however, have been hampered by lack of a suitable radioligand. Using a newly developed radioiodinated derivative of AVP with high specific activity and high affinity for the AVP V2-receptor (125I-[8-(p-(OH)-phenylpropionyl)]-LVP), we studied the role of AVP V2-receptors in CP-induced water retention. Male-Sprague-Dawley rats were treated orally with 40 mg CP/day or placebo for 7 days, after which Scatchard analysis was performed using membranes prepared from homogenized renal papilla. After oral water load, CP-treated rats but not control rats showed a significant decrease in plasma osmolality (289 ±2.2 to 284±0.8 mosmol/kg, p < 0.05). The Kd was 0.69 ± 0.16 nmol/l in controls and 0.70 ± 0.12 nmol/l after CP treatment (NS); Bmax was 129 ± 5.3 nmol/kg protein in controls (N = 8). Chlorpropamide significantly increased receptor density (Bmax) to 167±8.4 nmol/kg protein (N = 8) (p<0.05). Plasma AVP did not change significantly during CP treatment. These data show for the first time that CP in vivo increases the density of AVP V2 receptors without altering plasma AVP. This is associated with an impairment in water excretion. Our experiments and recent reports on CP-induced inhibition of AVP binding suggest that the AVP augmentation effect of CP is related to interference of CP with the AVP V2-receptor. Johannes Hensen, Department of Medicine I, Division of Endocrinology and Metabolism, Krankenhausstr. 12, 91054 Erlangen, Germany

Renal tubular vasopressin receptors downregulated by dehydration

1988 ◽  
Vol 254 (3) ◽  
pp. C404-C410 ◽  
Author(s):  
M. Steiner ◽  
M. I. Phillips
Keyword(s):  
Binding Sites ◽  
Plasma Osmolality ◽  
Fold Increase ◽  
Scatchard Analysis ◽  
Sprague Dawley ◽  
Single Class ◽  
Physiological Regulation ◽  
Lysine Vasopressin ◽  
Vasopressin Receptors ◽  
Renal Tubular

Receptors for arginine vasopressin (AVP) were characterized in tubular epithelial basolateral membranes (BL membranes) prepared from the kidneys of male Sprague-Dawley rats. Association of [3H]AVP was rapid, reversible, and specific. Saturation studies revealed a single class of saturable binding sites with a maximal binding (Bmax) of 184 +/- 15 fmol/mg protein and a KD of 0.61 +/- 0.04 nM. IC50S for AVP, lysine vasopressin, and oxytocin were 0.74 nM, 9.7 nM, and greater than 1 microM, respectively. The V2 receptor antagonist was more than 3,700 times as effective in displacing [3H]AVP than was the V1 antagonist. To investigate the physiological regulation of vasopressin receptors, the effects of elevated levels of circulating AVP on receptor characteristics were studied. Seventy-two-hour water deprivation significantly elevated plasma osmolality and caused an 11.5-fold increase in plasma [AVP]. Scatchard analysis revealed a 38% decrease in the number of AVP receptors on the BL membranes from dehydrated animals. The high-affinity binding sites on the BL membranes fit the pharmacological profile for adenylate cyclase-linked vasopressin receptors (V2), which mediate the antidiuretic action of the hormone. We conclude that physiologically elevated levels of AVP can downregulate vasopressin receptors in the kidney.

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.

Influence of steady-state PaCO2 on escape from ADH-induced water retention in the dog

1978 ◽  
Vol 234 (4) ◽  
pp. F291-F296
Author(s):  
W. D. Kaehny ◽  
A. Gougoux ◽  
J. J. Cohen
Keyword(s):  
Steady State ◽  
Water Intake ◽  
Water Deprivation ◽  
Water Retention ◽  
Plasma Osmolality ◽  
Similar Extent ◽  
Water Excretion ◽  
Average Value ◽  
Marked Disparity ◽  
Per Se

The influence of the prevailing PaCO2 on the water-retaining effects of sustained elevations in ADH was assessed by administering vasopressin (5 U in oil, twice daily) and a fixed water intake to dogs with eucapnia (n, 7), chronic hypercapnia (n, 6), and chronic hypocapnia (n, 8). Although water excretion initially fell to a similar extent in all three groups, cumulative water retention by day 4 of vasopressin administration was 77 mg/kg in the hypocapnic group, 46 ml/kg in the eucapnic group, and only 14 ml/kg in the hypercapnic group. These differences were reflected in a marked disparity in the degree of hyposmolality of body fluids, plasma osmolality falling by day 4 to an average value of 223, 237, and 268 mosmol/kg in the hypocapnic, eucapnic, and hypercapnic animals, respectively. In a separate group of dogs, water deprivation and water loading studies revealed that sustained hypercapnia does not affect the maximal concentrating or diluting ability of the kidney. We conclude, therefore, that the striking influence of the prevailing PaCO2 on the water-retaining effects of administered vasopressin cannot be ascribed to an altered responsiveness of the nephron per se, but that this influence reflects an alteration in the ease with which the kidney can escape from the antidiuretic effects of this substance.

Prolonged stimulation of intrarenal V1 vasopressin receptors results in sustained hypertension

1994 ◽  
Vol 267 (5) ◽  
pp. R1217-R1225 ◽  
Author(s):  
E. Szczepanska-Sadowska ◽  
K. Stepniakowski ◽  
M. M. Skelton ◽  
A. W. Cowley
Keyword(s):  
Arterial Pressure ◽  
Intravenous Administration ◽  
Plasma Osmolality ◽  
Sprague Dawley ◽  
Sustained Hypertension ◽  
Body Sodium ◽  
Chronic Infusion ◽  
Vasopressin Receptors ◽  
Stimulation Of ◽  
Interstitial Infusion

In an earlier study, we reported that chronic intravenous administration of the V1 agonist [Phe2,Ile3,Orn8]vasopressin (V1AG) results in sustained hypertension. The present study was designed to determine whether V1-induced hypertension may be related specifically to intrarenal actions of this peptide. Chronic infusion of the V1 agonist into the medullary interstitial space of a single remaining kidney of normal, conscious Sprague-Dawley rats at the rate of 2 ng.kg-1.min-1 for 14 days resulted in a sustained rise of 18 mmHg of mean arterial pressure (MAP). After withdrawal of V1AG, MAP returned to the baseline level. During the first day of V1AG infusion, there was a net loss of body sodium and no evidence of fluid retention throughout the period of hypertension. Plasma osmolality, sodium and potassium concentration, and water intake and body weight were not significantly affected by medullary interstitial infusion of V1AG. Renal medullary interstitial infusion of an equimolar amount of arginine vasopressin (AVP) did not affect MAP. Chronic medullary interstitial infusion of the selective V1 antagonist d(CH2)5[Tyr(Me)2,Ala-NH(2)9]AVP in equimolar amounts (2.5 ng.kg-1.min-1) prevented the MAP increase elicited by intravenous V1AG. However, intravenous administration of the V1 antagonist at the same rate together with V1AG (n = 7) failed to prevent hypertension. The results indicate that hypertension can be elicited by chronic stimulation of renal medullary V1 vasopressin receptors. They also suggest that some V2 agonistic properties of AVP may restrict the hypertensive action of this hormone. The mechanism for the rise of arterial pressure remains to be determined.

Hyponatraemia in quadriplegic patients

1988 ◽  
Vol 75 (4) ◽  
pp. 441-444 ◽  
Author(s):  
David J. Leehey ◽  
Alicia A. Picache ◽  
Gary L. Robertson
Keyword(s):  
Arginine Vasopressin ◽  
Fluid Intake ◽  
Plasma Osmolality ◽  
Free Water ◽  
Plasma Sodium ◽  
Free Water Clearance ◽  
Water Excretion ◽  
Water Load ◽  
Daily Urine ◽  
Plasma Arginine

1. Studies were performed in five hyponatraemic (plasma sodium 129 ±1.6 mmol/l; plasma osmolality 268 ±3.0 mosmol/kg) quadriplegic patients in order to elucidate its aetiology. Five age- and sex-matched healthy subjects served as controls. 2. Daily urine volumes were high (4454 ± 624 ml) in the quadriplegic patients secondary to habitually increased fluid intake. 3. All quadriplegic patients had suppressed plasma arginine vasopressin levels (< 0.8 pmol/l) and were able to form dilute urine after a water load (20 ml/kg). However, free water clearance and the ability to excrete the water load were frequently impaired, and these defects were associated with reductions in both osmolar clearance and delivery of filtrate to the distal diluting sites of the nephron. 4. During hypertonic saline (5%, w/v, NaCl) infusion, plasma arginine vasopressin rose progressively before plasma osmolality reached the normal range, consistent with a resetting of the osmostat. 5. We conclude that hyponatraemia in quadriplegic patients is related to an intrarenal defect in water excretion and resetting of the osmostat coupled with increased fluid intake.

THE DEVELOPMENT OF A RADIOIMMUNOASSAY FOR ARGININE-VASOPRESSIN: PRODUCTION OF ANTISERA AND LABELLED HORMONE; SEPARATION TECHNIQUES; SPECIFICITY AND SENSITIVITY OF THE ASSAY IN AQUEOUS SOLUTION

1972 ◽  
Vol 52 (2) ◽  
pp. 279-288 ◽  
Author(s):  
C. R. W. EDWARDS ◽  
T. CHARD ◽  
MURIEL J. KITAU ◽  
MARY L. FORSLING ◽  
J. LANDON
Keyword(s):  
Arginine Vasopressin ◽  
Specific Activity ◽  
Limit Of Detection ◽  
High Specific Activity ◽  
Ion Exchange Resin ◽  
Cross Reactivity ◽  
Amino Acid Sequences ◽  
Simple Method ◽  
Specificity And Sensitivity ◽  
Chloramine T

SUMMARY A radioimmunoassay for vasopressin was developed using antibodies produced against conjugated and non-conjugated arginine vasopressin. Despite the fact that the vasopressin molecule has only eight amino acids, cross reactivity studies showed that these antibodies were specific for different amino acid sequences. Labelled hormone of high specific activity (350–800 μCi/μg) was produced by a modification of the chloramine-T method. Unreacted iodide was removed by the batchwise addition of an ion-exchange resin. Other techniques of purification produced no advantage over this simple method. Several methods of separating antibody-bound and free hormone were studied. All except chromatoelectrophoresis proved satisfactory. Ammonium sulphate or ethanol precipitation of bound hormone was chosen because of simplicity, speed and reproducibility. The lower limit of detection of the assay was 80 pg arginine vasopressin/ml diluent buffer. Therefore an extraction and concentration procedure is necessary for the measurement of basal circulating levels of the hormone.

Thionamides and arsenite inhibit specific T3 binding to the hepatic nuclear receptor

1990 ◽  
Vol 68 (3) ◽  
pp. 616-621 ◽  
Author(s):  
Shinko Takagi ◽  
Brian C. W. Hummel ◽  
Paul G. Walfish
Keyword(s):  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Specific Activity ◽  
Binding Capacity ◽  
High Specific Activity ◽  
Relative Mass ◽  
Affinity Constant ◽  
Scatchard Analysis ◽  
Therapeutic Effects ◽  
Inhibitory Effects

Methimazole (MMI) and propylthiouracil (PTU) are widely used for the treatment of Graves' disease. However, no studies have been reported on the action of these drugs on binding of L-triiodothyronine (T3) to the nuclear receptor. T3 receptors of rat liver nuclei, prepared by differential centrifugation, were extracted with 0.4 M KCl and 5 mM dithiothreitol (DTT). In the assessment of T3 binding to the DTT-reduced receptor, the hepatic nuclear extract was chromatographed on Superose 6 to remove DTT and isolate proteins of relative mass ≈ 50 000 (chromatographed nuclear receptors (CNRs)), prior to the addition of [125I]T3 of high specific activity (3300 μCi/μg; 1 Ci = 37 GBq). MMI or PTU at 2 mM reduced specific T3 binding to CNR by 84% and 85%, respectively. The inhibitory effects of these reagents and 2 mM sodium arsenite (which complexes dithiols) were additive. Scatchard analyses indicated that neither MMI nor PTU (at 2 mM) significantly altered the affinity constant (Ka) (from 2.41 × 109 to 1.74 × 109 M−1 for PTU and 1.79 × 109 M−1 for MMI), while they both decreased (p < 0.02) maximal binding capacity (from 0.36 ± 0.02 to 0.19 ± 0.02 pmol/mg protein for MMI and 0.17 ± 0.02 pmol/mg protein for PTU). Dose-response curves showed that 50% inhibition was attained at 0.6 mM PTU or 1.0 mM MMI with ≈25% inhibition by both at 0.1 mM. Artefactual binding effects by MMI and PTU on [125I]T3 were excluded by chromatography experiments. Similar results were obtained using nuclear receptors prepared from livers of hyperthyroid rats. Pretreatment of CNR for 1 h with 5 mM methyl methanethiosulfonate (an oxidant of thiol groups) abolished the inhibitory effects of PTU, MMI, or arsenite, but was not inhibitory in itself. From these studies it is concluded that (i) MMI and PTU could exert at least part of their therapeutic effects by inhibiting specific binding of L-T3 to its hepatic nuclear receptor; (ii) these inhibitory effects of MMI and PTU are likely due to an interaction with cysteine residues (some of which are not in a dithiol configuration) that are essential for T3 binding to its receptor; and (iii) binding of T3 is not inhibited by oxidation of receptor thiols to methyl dithiol groups.Key words: nuclear triiodothyronine (T3) receptor, methimazole, propylthiouracil, Scatchard analysis.

RADIOIMMUNOASSAY OF [8-ARGININE]-VASOPRESSIN

1975 ◽  
Vol 80 (3) ◽  
pp. 444-452 ◽  
Author(s):  
P. Czernichow ◽  
U. Merkelbach ◽  
M. B. Vallotton
Keyword(s):  
Antidiuretic Hormone ◽  
Arginine Vasopressin ◽  
Association Constant ◽  
Specific Activity ◽  
Limit Of Detection ◽  
High Specific Activity ◽  
High Association ◽  
Theoretical Maximum

ABSTRACT A radioimmunological method for the determination of the human antidiuretic hormone, [8-arginine]-vasopressin (AVP), is described in detail. The antiserum has been raised in rabbits injected with AVP adsorbed onto charcoal particles and is used at a final dilution of 1:200 000. It contains antibodies directed specifically against the C-terminal tripeptide and possesses a high association constant of 8.2× 1012 1/mole. AVP is labelled in monoiodinated form (as proven after pronase digestion) at a high specific activity close to the theoretical maximum after purification from unlabelled hormone on Sephadex gel. The standard curves are characterized by a Bo of 55 %, a limit of detection ascertained at least at 3 pg (10 % displacement) and a 50 % displacement achieved with 35.5 pg. The index of precision λ ranges from 0.033 to 0.042. The conditions of the assay (buffer's composition and pH, timing) were systematically varied and tested. In addition the result of immunization of chicken with AVP is reported. The assay is adequate for the measurement of AVP in urine and plasma and will be described in forthcoming papers.

Osmoregulation in pseudopregnant and prolactin-treated rats: comparison with normal gestation

1988 ◽  
Vol 254 (3) ◽  
pp. R478-R484 ◽  
Author(s):  
W. M. Barron ◽  
M. D. Lindheimer
Keyword(s):  
Arginine Vasopressin ◽  
Plasma Osmolality ◽  
Plasma Sodium ◽  
Minimal Effect ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Sprague Dawley Rats ◽  
Plasma Arginine ◽  
Normal Gestation

Osmoregulation was studied throughout rodent pregnancy focusing on the importance of the fetoplacental unit and prolactin in the observed alterations. Plasma osmolality (Posmol) and plasma sodium (PNa), similar in 8-day gravid and virgin Sprague-Dawley rats, decreased significantly by gestational day 10, reaching a nadir 8-10 mosmol/kg and 3-5 meq/l, respectively, below virgin levels by day 14 (both P less than 0.001). Despite this, plasma arginine vasopressin (PAVP) was measurable and similar in all pregnant and virgin groups. Osmotic thresholds for arginine vasopressin (AVP) secretion, similar in 8-day gravid and virgin rats, decreased 7.7 and 10.7 mosmol/kg in 12- and 14-day pregnant rats, respectively (both P less than 0.001). In contrast, Posmol decreased less than 2 mosmol/kg in 12- to 14-day pseudopregnant animals. When pseudopregnancy was prolonged to 18 days by prior hysterectomy, Posmol was only 2.6 mosmol/kg below that of cycling, hysterectomized controls. In other studies 14 days of hyperprolactinemia evoked by estradiol or treatment with ovine or rat prolactin had minimal effect on Posmol. We conclude that parallel decrements in Posmol and osmotic thresholds for AVP release occur during early rodent pregnancy, alterations that cannot be explained by gestational increases in circulating prolactin. In addition, the failure of pseudopregnancy. to mimic the hypotonicity of gestation suggests an important role for the fetoplacental unit in the osmoregulatory changes of rat pregnancy.

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.

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