Angiotensin-(1-7) serves as an aquaretic by increasing water intake and diuresis in association with downregulation of aquaporin-1 during pregnancy in rats

2008 ◽  
Vol 294 (3) ◽  
pp. R1073-R1080 ◽  
Author(s):  
J. Joyner ◽  
L. A. A. Neves ◽  
K. Stovall ◽  
C. M. Ferrario ◽  
K. B. Brosnihan

We previously demonstrated that kidney and urine levels of angiotensin-(1-7) [ANG-(1-7)] were increased in pregnancy. To explore the role of ANG-(1-7) on fluid and electrolyte homeostasis during pregnancy, we evaluated the effect of the ANG-(1-7) antagonist d-alanine-[ANG-(1-7)] (A-779) on kidney function. Virgin and pregnant rats received infusion of vehicle or A-779 (48 μg·kg−1·h−1) for 8 days by osmotic minipumps. Metabolic studies were done on treatment day 7–8. Virgin and pregnant rats at day 15 and 19 were killed, and blood and kidneys were collected. Kidneys were prepared for Western blot analysis for aquaporin-1 (AQP1) and aquaporin-2. In virgin female rats, A-779 increased urine volume and decreased urinary osmolality and AQP1 with no change in water intake. In 19-day pregnant rats, A-779 significantly decreased water intake and urine volume and increased urinary osmolality and kidney AQP1 expression. Only in late gestation did A-779 treatment decrease the difference between intake and output (balance). A-779 treatment increased plasma vasopressin in late gestation but did not change vasopressin in virgins. In virgin and pregnant animals, A-779 administration had no effect on blood pressure, plasma volume, blood volume, or urinary electrolytes. These results suggest that ANG-(1-7) produces antidiuresis associated with upregulation of AQP1 in virgin rats, whereas ANG-(1-7) produces diuresis in late gestation with downregulation of AQP1. ANG-(1-7) contributes to the enhanced water intake during pregnancy, allowing maintenance of the normal volume-expanded state despite diuresis produced in part by decreased AVP and AQP1.

1999 ◽  
Vol 96 (4) ◽  
pp. 427-430 ◽  
Author(s):  
M. BLUM ◽  
Y. WEISMAN ◽  
S. TURGEMAN ◽  
S. CABILI ◽  
Y. WOLLMAN ◽  
...  

Normal pregnancy is associated with an increase in serum parathyroid hormone and 1,25-dihydroxyvitamin D3 (calcitriol). The effect of pregnancy on these hormones in chronic renal failure (CRF) is unknown. The present work was undertaken to study the changes of serum immunoreactive parathyroid hormone (iPTH) and calcitriol in pregnant rats with CRF. The following experimental groups were studied: CRF1 (5/6 nephrectomized virgin female rats), CRF2 (5/6 nephrectomized pregnant rats at day 20–21 of pregnancy), CRF3 (5/6 nephrectomized rats 2 weeks after delivery) and their respective sham-operated control groups: N1, N2 and N3. The 5/6 nephrectomy (CRF1) resulted in renal failure with very high serum iPTH (100±18 pg/ml) and low calcitriol levels (10.6±4.3 pg/ml) compared with normal rats [N1: 14±2.5 pg/ml (P< 0.001) and 18.2±4.2 pg/ml (P< 0.01) respectively]. The pregnancy in CRF rats (CRF2) resulted in normalization of serum iPTH levels (18.2±5.41 pg/ml), which was associated with a parallel increase in serum calcitriol (29.4±8.0 pg/ml) similar to that in pregnancy of normal rats (N2). Two weeks after delivery the CRF rats (CRF3) once again had high serum iPTH (87±17 pg/ml) and low calcitriol levels (9.3±1.2 pg/ml), similar to those observed in non-pregnant uraemic rats (CRF1). It is concluded that pregnancy decreases serum iPTH in 5/6 nephrectomized CRF rats most probably by the increased level of calcitriol synthesized by the feto-placental unit.


1957 ◽  
Vol 35 (1) ◽  
pp. 1183-1188
Author(s):  
O. H. Gaebler ◽  
Rachel Glovinsky ◽  
Helen Lees ◽  
Trieste Vitti

The losses of weight and nitrogen produced by daily doses of corticotropin (20 units), hydrocortisone acetate (15 mg.), and prednisone (10 mg.) were studied in normal bitches receiving a constant amount of food equal to that which before therapy had either maintained weight or permitted it to increase slowly. Loss of weight during therapy was accompanied by a decrease in the difference between water intake and urine volume, regardless of whether water intake rose or fell. Weight was restored fairly soon after cessation of therapy with prednisone, but not after corticotropin or hydrocortisone. The probability that calorigenic effects of these substances were involved is discussed. Aspirin (20 grains daily) increased nitrogen output, but weight, as well as the difference between water intake and urine volume, increased. The pattern of response to each of the compounds, was, in general, quite similar, but varied in detail in different animals or experiments. Effects of applying hydrocortisone ointment to affected areas in a bitch with dermatitis are also recorded. Prompt improvement was accompanied by losses of weight and nitrogen. Other instances in which the local and general effects of a hormone appear to be contradictory are cited.


1999 ◽  
Vol 277 (2) ◽  
pp. R532-R540 ◽  
Author(s):  
Kathleen S. Curtis ◽  
J. Thomas Cunningham ◽  
Cheryl M. Heesch

Fos and dopamine β-hydroxylase immunoreactivity were evaluated in the brain stems of 21-day pregnant and virgin female rats injected with either hydralazine (HDZ; 10 mg/kg iv) or vehicle. HDZ produced significant hypotension in both groups, although baseline blood pressure was lower in pregnant rats (96 ± 2.5 mmHg) than in virgin female rats (121 ± 2.8 mmHg). There were no differences in Fos immunoreactivity in the brain stems of pregnant and virgin female rats after vehicle treatment. HDZ-induced hypotension significantly increased Fos expression in both groups; however, the magnitude of the increases differed in the caudal ventrolateral medulla (CVL), the area postrema (AP), and the rostral ventrolateral medulla (RVL). Fos expression after HDZ in pregnant rats was augmented in noncatecholaminergic neurons of the CVL but was attenuated in the AP and in noncatecholaminergic neurons in the RVL. These results are consistent with differences in the sympathetic response to hypotension between pregnant and virgin female rats and indicate that the central response to hypotension may be different in pregnant rats.


1957 ◽  
Vol 35 (12) ◽  
pp. 1183-1188 ◽  
Author(s):  
O. H. Gaebler ◽  
Rachel Glovinsky ◽  
Helen Lees ◽  
Trieste Vitti

The losses of weight and nitrogen produced by daily doses of corticotropin (20 units), hydrocortisone acetate (15 mg.), and prednisone (10 mg.) were studied in normal bitches receiving a constant amount of food equal to that which before therapy had either maintained weight or permitted it to increase slowly. Loss of weight during therapy was accompanied by a decrease in the difference between water intake and urine volume, regardless of whether water intake rose or fell. Weight was restored fairly soon after cessation of therapy with prednisone, but not after corticotropin or hydrocortisone. The probability that calorigenic effects of these substances were involved is discussed. Aspirin (20 grains daily) increased nitrogen output, but weight, as well as the difference between water intake and urine volume, increased. The pattern of response to each of the compounds, was, in general, quite similar, but varied in detail in different animals or experiments. Effects of applying hydrocortisone ointment to affected areas in a bitch with dermatitis are also recorded. Prompt improvement was accompanied by losses of weight and nitrogen. Other instances in which the local and general effects of a hormone appear to be contradictory are cited.


1977 ◽  
Vol 75 (3) ◽  
pp. 373-382 ◽  
Author(s):  
JEAN-MICHEL GAREL ◽  
ANNICK JULLIENNE

A radioimmunoassay for rat calcitonin was developed, which used a heterologous system that involved labelled human calcitonin, an antibody developed against purified human calcitonin and purified or synthetic rat calcitonin as a standard. The sensitivity of the assay was 0·3 ng rat calcitonin/ml plasma. The levels of calcitonin in the plasma of pregnant rats were studied in the last week of gestation and compared with the levels found in the plasma of control virgin female rats. The level of calcitonin in the plasma after 17·5 days of gestation was already higher than that in the control rats, it increased further up to 19·5 days and decreased at 21·5 days. Infusion of calcium into pregnant rats for 1 h after 21·5 days of gestation induced a sixfold increase in the level of calcitonin in the plasma after 30 min, and a threefold increase after 1 h. The level of calcitonin in the plasma of fed and unfed newborn rats was measured 2, 6, 12 and 16 h after birth. At each stage, the concentration of calcitonin was higher in fed than in unfed animals. Stomach gavage of fat (triglycerides) in fasted rats born 2 h earlier stimulated secretion of calcitonin; administration of pentagastrin or glucagon had no effect on the level of calcitonin in the plasma. Subcutaneous injection of a calcium load to fasted newborn rats (2 hours old) increased the level of calcitonin in the plasma after 30 min. These results demonstrate that during gestation calcitonin has a comparable role in rats to that already found in ruminants. They also substantiate the part played by the fat present in milk as a stimulus (through some unknown gastrointestinal hormones) for secretion of calcitonin during suckling, and the involvement of calcitonin secretion in the regulation of nutrient absorption in the newborn rat.


2004 ◽  
Vol 287 (2) ◽  
pp. R277-R283 ◽  
Author(s):  
Daniel S. Knee ◽  
Aileen K. Sato ◽  
Catherine F. T. Uyehara ◽  
John R. Claybaugh

Chronic consumption of ethanol in adult rats and humans leads to reduced AVP-producing neurons, and prenatal ethanol (PE) exposure has been reported to cause changes in the morphology of AVP-producing cells in the suprachiasmatic nucleus of young rats. The present studies further characterize the effects of PE exposure on AVP in the young adult rat, its hypothalamic synthesis, pituitary storage, and osmotically stimulated release. Pregnant rats were fed a liquid diet with 35% of the calories from ethanol or a control liquid diet for days 7–22 of pregnancy. Water consumption and urine excretion rate were measured in the offspring at 60–68 days of age. Subsequently, the offspring were infused with 5% NaCl at 0.05 ml·kg−1·min−1 with plasma samples taken before and at three 40-min intervals during infusion for measurement of AVP and osmolality. Urine output and water intake were ∼20% greater in PE-exposed rats than in rats with no PE exposure, and female rats had a greater water intake than males. The relationship between plasma osmolality and AVP in PE-exposed rats was parallel to, but shifted to the right of, the control rats, indicating an increase in osmotic threshold for AVP release. Pituitary AVP was reduced by 13% and hypothalamic AVP mRNA content was reduced by 35% in PE-exposed rats. Our data suggest that PE exposure can cause a permanent condition of a mild partial central diabetes insipidus.


2020 ◽  
Vol 150 (5) ◽  
pp. 1068-1075 ◽  
Author(s):  
Margaret E Brosnan ◽  
Garrett Tingley ◽  
Luke MacMillan ◽  
Brian Harnett ◽  
Theerawat Pongnopparat ◽  
...  

ABSTRACT Background Formate can be incorporated into 10-formyl-tetrahydrofolate (10-formyl-THF), which is a substrate for purine synthesis, and after further reduction of the one-carbon group, may be used as a substrate for thymidylate synthesis and for homocysteine remethylation. Objective We examined plasma formate concentrations and the expression of genes involved in the production and utilization of formate in fetal and neonatal rats and in pregnant and virgin female rats. Methods In 1 experiment, plasma formate was measured by GC-MS in rats aged 1–56 d. In a second experiment, virgin female (adult) rats, 19-d pregnant rats (P) and their male and female fetuses (F), and 3-d-old (N) and 7-d-old (J) offspring had plasma and amniotic fluid analyzed for formate by GC-MS, mRNA abundance in liver and placenta by qPCR, and several plasma amino acids by HPLC. Results The plasma formate concentration was significantly higher in fetuses at embryonic day 19 than in the mothers. It was also significantly higher in neonatal rats but slowly returned to adult concentrations by ∼3 wk. The abundance of mitochondrial monofunctional 10-formyl-tetrahydrofolate synthetase (Mthfd1l) mRNA was significantly higher in placenta (PP) and F liver than in liver of N or J. Expression of mitochondrial bifunctional NAD-dependent methylene-tetrahydrofolate dehydrogenase/methenyl-tetrahydrofolate cyclohydrolase (Mthfd2) was significantly enriched in PP and liver of P, intermediate in F liver, and much lower in liver of N and J, relative to PP. Serine hydroxymethyltransferase 2 (Shmt2), methylenetetrahydrofolate dehydrogenase 1 (Mthfd1), and glycine decarboxylase protein of the glycine cleavage system (Gldc) mRNA expression was significantly lower in PP compared with other groups. Cytoplasmic NAD(P)-dependent 10-formyl-tetrahydrofolate dehydrogenase (Aldh1/1) and mitochondrial NAD(P)-dependent 10-formyl-tetrahydrofolate dehydrogenase (Aldh1/2) , genes responsible for the catabolism of 10-formylTHF, were very weakly expressed in PP, low in livers of F and N, and reached the significantly higher adult levels in J. Serine, glycine, and methionine concentrations in plasma of F were significantly higher than in plasma of P. Conclusions Formate metabolism is highly active in fetuses and in placenta of pregnant rats.


2009 ◽  
Vol 28 (4) ◽  
pp. 266-277 ◽  
Author(s):  
M. Gary I. Riley ◽  
Raymond G. York

Salcaprozate sodium (SNAC) (sodium 8-((2-hydroxybenzoyl) amino) octanoate, CAS RN 203787-91-1) is classified as an oral absorption promoter and may be a useful means for improving the absorption of certain nutrients and pharmaceutical agents. Presented herein is a subset of data from a larger study evaluating the potential effects of SNAC on the gestation, parturition, lactation, maternal behavior, and offspring development of rats. Pregnant Crl:CD BR VAF/Plus female rats (F0; n = 25) received SNAC at 1000 mg/kg/d orally (gavage) from implantation through lactation and weaning. F1 pups were exposed in utero and potentially through maternal milk; observations continued through sexual maturity. The study concluded with Caesarean sectioning of F1 dams for litter observations and fetal evaluations. No deaths, abortions, premature deliveries, or gross lesions occurred in (F0) dams. Excess salivation, red perivaginal substance, and slight reductions in body weights, body weight gains, and/or feed intake were noted in late gestation/early lactation. SNAC was associated with a prolonged gestation period, leading to a greater number of dams with stillborn pups, higher number of stillborn pups, and reduced live litter size. Offspring body weights/gains, feed consumption, age of sexual maturation, mating, fertility, behavioral parameters, and organ weights at necropsy were unaffected by SNAC. No gross external changes were observed in F1 or F2 pups. In summary, SNAC administered orally at 1000 mg/kg/d to pregnant rats from gestation to weaning resulted in a slight decrease in maternal body weights (−3.8%) and prolonged gestation, along with an increase in stillbirths, but had no effects on growth and development in surviving offspring.


1986 ◽  
Vol 250 (4) ◽  
pp. E377-E380
Author(s):  
Y. Hitier ◽  
O. Champigny ◽  
G. Bourdel

In virgin female rats thioacetamide administration (1 mg/100 g body wt) induced a 16-fold increase in liver ornithine decarboxylase (ODC) activity and a significant decrease (19%) in hepatic urea concentration. The ornithine-metabolizing enzymes, ornithine-oxo-acid aminotransferase and ornithine carbamoyltransferase, were not modified by the treatment; only carbamoyltransferase, were not modified by the treatment; only carbamoyl-phosphate synthetase I activity was significantly reduced. In 19-day pregnant rats DL-alpha-difluoromethylornithine treatment inhibited the expression of enhanced ODC activity occurring normally at this stage of pregnancy. Concomitantly an inhibition of the usual decrease in hepatic urea was observed. This increase of ureagenesis occurred without any increase in liver N-acetylglutamate or ornithine concentrations, which remained as low as in normal pregnant rats.


1993 ◽  
Vol 265 (4) ◽  
pp. R902-R906 ◽  
Author(s):  
S. Kaufman ◽  
Y. Deng

Chronic indwelling balloons were placed at the junction of the right atrium and the right superior vena cava of virgin female rats. The renal response to discrete standardized atrial stretch was tested in the conscious animals. The rats were then mated, and the renal response was retested at days 7, 14, and 20 of pregnancy. On day 21, the rats were killed, and the pressure-volume relationship of the right atria was measured. In response to atrial stretch, there was an increase in urine volume, urine sodium output, and urine potassium output and a decrease in free water clearance in the virgin rats. Subsequent to mating, these responses were completely abolished at all stages of pregnancy. The renal responses to atrial stretch were also abolished during pseudopregnancy. Central venous pressure did not change when the intracardiac balloons were inflated; there were also no changes in resting central venous pressure during pregnancy. There were no significant changes in unstressed atrial volume or in atrial compliance during pregnancy.


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