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G A Schuiling

Publications and source records attributed to G A Schuiling.

At least 19 recordsLinked to original sources
PubMed1999

Pregnancy enhances the sensitivity of glomerular ecto-adenosine triphosphate-diphosphohydrolase to products of activated polymorphonuclear leukocytes.

To test the hypothesis that pregnancy enhances the sensitivity of glomerular ecto-adenosine triphosphate-diphosphohydrolase to products of activated polymorphonuclear leukocytes, cryostat-cut kidney sections of pregnant and cycling rats were exposed to activated polymorphonuclear leukocytes and subsequently stained for ecto-adenosine triphosphate-diphosphohydrolase activity. The results show that the levels of ecto-adenosine triphosphate-diphosphohydrolase activity of pregnant rats showed a significantly greater decrease after incubation with activated polymorphonuclear leukocytes than did those of cycling rats.

Adenosine Triphosphatases↗
PubMed1999

Pregnancy aggravates proteinuria in subclinical glomerulonephritis in the rat.

Because subclinical renal disease may be aggravated during pregnancy--as reflected in the occurrence of proteinuria, for example--we investigated whether a subclinical glomerulonephritis (SG) in the non-pregnant rat (passive Heymann nephritis), a condition without proteinuria, is aggravated when the animals become pregnant and, if so, whether this is associated with a glomerular inflammatory reaction. SG was induced in non-pregnant rats 8 days before pregnancy. On day -1, part of the group of rats became pregnant. Three experiments were performed. In experiment 1, 4-hour urine albumin excretions and blood pressure (tail cuff) were measured. In experiment 2, the glomerular filtration rate (GFR) was measured with the chromium 51-labeled ethylenediaminetetraacetic acid method, while in experiment 3, parameters characteristic of a glomerular inflammation were studied. Experiment 1 revealed that non-pregnant rats with SG did not exhibit proteinuria. However, after the rats became pregnant, a significant proteinuria occurred, without an increase in systolic blood pressure. Experiment 2 revealed that the GFR did not increase in pregnant rats with SG, while experiment 3 showed that only pregnant animals exhibited a significant glomerular inflammation; this glomerular inflammation was characterized by intraglomerular influx of polymorphonuclear cells and monocytes. The results suggest that an SG in the rat may flare up during pregnancy. This exacerbation is characterized by proteinuria and coincides with a glomerular inflammatory reaction. It is suggested that proteinuria and the glomerular inflammatory reaction are causally related and promoted by the pregnant condition.

Albuminuria↗
PubMed1999

FSH inhibits the augmentation by oestradiol of the pituitary responsiveness to GnRH in the female rat.

The effect of follicle stimulating hormone (FSH) treatment on the pituitary response to gonadotrophin-releasing hormone (GnRH) was studied in rats in various reproductive conditions. A 3-day treatment of cycling rats with FSH (Metrodin; 10 IU/injection) lowered the spontaneous pre-ovulatory. LH-surge and suppressed the pituitary luteinizing hormone (LH) response to GnRH. FSH also suppressed the LH response of pseudopregnant (PSP) rats on day 8 of pseudopregnancy, but not that of day-8 PSP rats which had been ovariectomized on day 4 (OVX-PSP rats). GnRH induced self priming in cycling, PSP and OVX-PSP rats. Oestradiol strongly augmented the pituitary LH-response to GnRH injection in PSP and OVX-PSP rats, but not in cycling rats; probably because in these latter animals the LH response to GnRH was already augmented by endogenous oestradiol. FSH suppressed the LH response to GnRH in oestradiol-treated PSP and cycling rats; in these latter rats the suppression of the LH response was as strong as that in cycling rats not treated with oestradiol. FSH did not suppress the LH response of oestradiol-treated OVX-PSP rats. The effect of FSH was not associated with changes in plasma oestradiol and progesterone concentrations. Analysis of the data revealed that FSH specifically suppressed the augmentative effect of oestradiol, but did not affect the GnRH-self priming effect. It is concluded that under the influence of FSH, the ovaries produce a factor which suppresses the augmentative effect of oestradiol on the GnRH-induced LH response of the pituitary gland. It is suggested that this effect of FSH underlies the suppression of the spontaneous LH-surges of FSH-treated cycling rats. As the present putative 'oestrogen-antagonizing factor' did not suppress the GnRH-self priming effect, it is suggested that this factor is not identical to gonadotrophin surge inhibiting factor.

Animals↗
PubMed1999

Effect of estradiol and progesterone on the low-dose endotoxin-induced glomerular inflammatory response of the female rat.

PROBLEM: Is the endotoxin-induced glomerular inflammatory response of the female rat under ovarian control? METHOD OF STUDY: Ovariectomized rats (OVX), with or without progesterone (OVX-P) or estradiol (OVX-E) treatment, as well as rats in the follicular or luteal phase of the ovulatory cycle were infused with endotoxin or saline and sacrificed 3 days later. Cryostat kidney sections were immunohistologically stained for the presence of neutrophils and monocytes (MO) and the expression of adhesion molecules. RESULTS: After endotoxin, the glomerular number of neutrophils and the number of MAC-1 positive cells were increased in luteal-phase and in OVX-P rats, and the number of glomerular Mø was increased in luteal-phase, OVX, OVX-E, and OVX-P rats. Endotoxin increased ICAM-1 expression in all groups of rats, except in follicular-phase rats. The glomerular number of LFA-1- and VLA-4 positive cells following endotoxin were only increased in OVX rats. CONCLUSIONS: It is concluded that endotoxin-induced monocyte infiltration and ICAM-1 expression are inhibited by a factor produced during the follicular phase, probably by developing follicles. Infiltration of neutrophils and expression of MAC-1, LFA-1, VLA-4 seem to be under control of progesterone or estradiol.

Animals↗
PubMed1999

Progesterone stimulates pancreatic cell proliferation in vivo.

Treatment of cyclic and pregnant rats with progesterone stimulates cell proliferation within the islets of Langerhans. It was investigated whether this effect of progesterone depends on sex and/or the presence of the gonads or the presence of oestradiol. For this purpose, Silastic tubes containing progesterone were inserted s.c. in intact and gonadectomized male and female rats, and in gonadectomized female rats treated with oestradiol. After 6 days of progesterone treatment, rats were infused for 24 h with 5-bromo-2'-deoxyuridine (BrdU) and dividing cells were identified in pancreatic sections by immunostaining for BrdU. Progesterone treatment increased islet-cell proliferation in intact male and female rats (P < 0.05), but not in gonadectomized male and female rats or in gonadectomized female rats supplemented with oestradiol. Furthermore, in intact male and female rats, progesterone treatment also stimulated cell proliferation in extra-islet pancreatic tissue (P < 0.05). Identification of the proliferating cells, by double-immunocytochemistry, revealed that progesterone treatment stimulated proliferation of both alpha and beta cells within the pancreatic islets. In extra-islet pancreatic tissue, progesterone treatment stimulated proliferation in both duct (cytokeratin 20-immunoreactive) and non-duct cells. Progesterone treatment did not increase the number of single glucagon or insulin-containing cells outside the pancreatic islets, nor that of cytokeratin 20/insulin double-positive cells, suggesting that progesterone treatment did not stimulate differentiation of duct cells into endocrine cells. Progesterone treatment did not affect insulin responses to an i.v. glucose load (0.5 g/kg body weight). It is concluded that progesterone stimulates pancreatic cell proliferation indirectly; gonadal factor(s), not identical to oestradiol, is (are) probably involved.

20-alpha-Dihydroprogesterone↗
PubMed1998

Glucose consumption by various tissues in pregnant rats: effects of a 6-day euglycaemic hyperinsulinaemic clamp.

In the course of pregnancy maternal tissues become increasingly more insensitive to insulin. As 6 days of euglycaemic hyperinsulinaemic clamping, from day 8 until 14 of gestation, ameliorates total glucose consumption, we analysed the contribution of individual tissues in this phenomenon. We measured not only glucose consumption, but also concentrations of the glucose transporter protein GLUT4 in selected tissues. On day 15 of pregnancy in saline-infused (pregnant control) rats, 18F-fluoro-2-deoxy-D-glucose (FDG) consumption, as measured by positron emission tomography, as well as GLUT4 content were diminished in heart (P < 0.05), and in brown (P < 0.05) and white adipose tissues (P < 0.05) when compared with non-pregnant controls. During clamping, on day 13 of the experiments, both in pregnant and non-pregnant rats FDG consumption was increased in liver (P < 0.05), skeletal muscle (P < 0.05), brown (P < 0.05) and white adipose tissues (P < 0.05) when compared with saline-infused controls. In both the reproductive conditions, only in white adipose tissue was this increased FDG consumption associated with increased GLUT4 levels (P < 0.05); GLUT4 content of m. gastrocnemius, m. soleus, heart and brown adipose tissue was unaffected by clamping. In non-pregnant rats, 24 h after clamping ceased, FDG consumption was diminished in heart compared with control non-pregnant rats (P < 0.05). In pregnant rats, however, 24 h after clamping (i.e. day 15 of pregnancy) both FDG consumption (P < 0.05) and GLUT4 content (P < 0.05) were still increased in white adipose tissue only, when compared with saline-infused pregnant rats on the same day of gestation. It is suggested that hyperinsulinaemic euglycaemic clamping ameliorates insulin action halfway pregnancy, in particular by stimulation of glucose consumption and GLUT4 protein content in white adipose tissue.

Adaptation, Physiological↗
PubMed1998

Proliferation of pancreatic islet-cells in cyclic and pregnant rats after treatment with progesterone.

The effect of progesterone (P) on pancreatic islet-cell proliferation and function of cyclic and pregnant rats was investigated in vivo. Silastic tubes containing P were inserted s.c. in cyclic rats for 7 or 14 days and in pregnant rats from day 7 to 14, from day 14 to 21 or from day 7 to 21 of pregnancy. 5-Bromo-2-deoxyuridine (BrdU) was infused during the last 24h of the treatment; the proportion of dividing islet-cells was determined in pancreatic sections, which were immunostained for BrdU. Islet-cell function was determined by measuring glucose and insulin response to a standard intravenous glucose challenge. P treatment increased P and 20alpha-dihydroprogesterone (20alpha-OHP) levels in cyclic rats; in pregnant rats, only the plasma levels of 20alpha-OHP were elevated. Both 7 and 14 days of P treatment stimulated islet-cell proliferation in cyclic rats. In pregnant rats, P treatment increased islet-cell proliferation on day 14, but not on day 21 after either 7 or 14 days of P treatment. P did not affect plasma lactogenic activity in pregnant rats; plasma concentrations of prolactin were decreased after 14 days of P treatment in cyclic rats, but were not affected in pregnant rats. P treatment had no effect on glucose tolerance and glucose-stimulated insulin secretion in any of the groups. It was concluded that: 1. in vivo P stimulates islet-cell proliferation, but does not affect islet-cell function, 2. the stimulatory effects of P are indirect and possibly mediated by the P metabolite 20alpha-OHP and 3. at the end of gestation, stimulation of islet-cell proliferation is inhibited by some factor, which is not identical to P.

Algestone↗
PubMed1998

Superoxide-mediated glomerulopathy in the endotoxin-treated pregnant rat.

In the present study the role of superoxide in the glomerular damage in the low-dose endotoxin-infused pregnant rats was investigated. On day 14 of pregnancy, 12 rats were infused for 1 h with 1.0 microgram/kg bw endotoxin via a permanent jugular vein cannula. Of these rats, 6 were treated with SOD both prior to endotoxin infusion (7,000 U/kg) and 30 min (7,000 U/kg) and 4 h (14,000 U/kg) after the start of the infusion (SOD rats). The other 6 rats received no SOD treatment (endotoxin rats). Control pregnant rats were infused for 1 h with saline (saline rats; n = 6). Urinary albumin was measured on days 15 and 19 of pregnancy. On day 21, rats were sacrificed and kidney specimens were snap-frozen. Cryostat kidney sections were stained for fibrinogen, ecto-ATP diphosphohydrolase (e-ATPase) activity, polymorphonuclear cells, monocytes and various adhesion molecules on the endothelium and the leukocytes. SOD treatment appeared to significantly prevent the increased urinary albumin excretion and the decrease of glomerular e-ATPase activity which were observed in endotoxin-treated rats. This effect of SOD treatment after endotoxin infusion was associated with a significant inhibition of glomerular monocyte influx and a significant inhibition of adhesion molecule expression (glomerular ICAM-1 and VCAM-1 and leukocyte LFA-1 and VLA-4). The present data suggest that in the endotoxin-infused pregnant rat, production of superoxide in the first few hours after the infusion plays a role in the induction of glomerular damage, leading to albuminuria and diminished e-ATPase expression during the following days.

Adenosine Triphosphatases↗
PubMed1997

Plasma endothelin-1 and tumor necrosis factor-alpha concentrations in pregnant and cyclic rats after low-dose endotoxin infusion.

Plasma endothelin-1 and tumor necrosis factor-alpha were determined in pregnant and cyclic rats after infusion of either endotoxin (1.0 microgram/kg of body weight) or saline solution. After endotoxin, but not after saline solution, administration there was a transient endothelin-1 response in pregnant rats but not cyclic rats. In both reproductive conditions there was an equally high transient tumor necrosis factor-alpha response after endotoxin.

Animals↗
PubMed1997

Aspirin treatment of the low-dose-endotoxin-treated pregnant rat: pathophysiologic and immunohistologic aspects.

In the present study, we evaluated the effect of low-dose aspirin (acetylsalicylic acid (ASA); 1.0 mg/kg daily) on blood pressure, albumin excretion, glomerular fibrinogen deposits, and glomerular (basement) membrane-bound adenosine diphosphatase (ecto-ADPase) activity, as well as on glomerular inflammation in pregnant rats infused with low-dose endotoxin (1.0 mg/kg). Rats (day 14 of pregnancy) were infused with endotoxin (ET rats) or saline (control rats) and received ASA in their drinking water. These rats were compared with non-ASA-treated rats. Blood pressure and albumin excretion were measured from day 15 to day 21, and glomerular fibrinogen and ecto-ADPase activity were measured at day 21. Glomerular inflammation was evaluated at various times after the start of the infusion. The results show that treatment with ASA had a significant beneficial effect on hypertension and inflammation induced by endotoxin in pregnant rats, whereas it reduced albumin excretion and glomerular fibrinogen deposits in some of the rats.

Albuminuria↗
PubMed1997

Role of increased insulin demand in the adaptation of the endocrine pancreas to pregnancy.

During gestation the demand for insulin increases due to a decrease in insulin sensitivity of the maternal tissues. Simultaneously, pancreatic islet-cell proliferation, as well as insulin production and secretion increase. Both phenomena appear to be caused by the actions of pregnancy hormones. We studied the relationship between the two phenomena by investigating whether the supply of exogenous insulin affects the secretion of pregnancy hormones and islet function during gestation. For that purpose rats were treated with high doses of insulin (4.8 IU day-1 by sub-cutaneous osmotic mini pumps) so that the endogenous demand for insulin was fully satisfied from day 8-14 of gestation. Euglycaemia (5.0 mM) was maintained by intra venous infusion of glucose. The treatment suppressed insulin synthesis, as measured by in situ hybridization, in both pregnant and cyclic rats. In addition, in pregnant rats the increments in insulin secretion and in islet-cell proliferation were partly prevented. Furthermore, the data also suggest that in pregnant rats the treatment partly prevented the decrease in insulin sensitivity. Finally, the treatment did not affect the plasma concentrations of progesterone, prolactin and placental lactogen, but prevented the rise in growth hormone concentrations in pregnant rats. The present data suggest that, next to direct effects of pregnancy hormones and growth hormone on the pancreatic islets, a decreased insulin sensitivity in the maternal tissues, induced by actions of the same hormones, is involved in the regulation of islet function during gestation.

Adaptation, Physiological↗
PubMed1997

Reproductive condition and the low-dose endotoxin-induced inflammatory response in rats. Glomerular influx of inflammatory cells and expression of adhesion molecules.

These experiments were designed to study the increased sensitivity of pregnant rats to endotoxin. Pregnant (Pr), cyclic (C), and progesterone (P)-treated pseudopregnant rats with or without a decidualized uterus (PSP and DEC rats, respectively) received infusions of an ultra-low dose of endotoxin (1.0 microg/kg BW) and were killed 3 days later. Pr, PSP, and DEC rats were infused on Day 14, C rats on diestrus. Endotoxin-infused rats were compared with saline-infused rats in the same reproductive conditions. The inflammatory reaction of the glomeruli of the kidneys was studied by immunohistochemical methods using 4-microm cryostat sections stained with specific monoclonal antibodies against neutrophils (polymorphonuclear cells, PMNs) and monocytes (MOs), and against the adhesion molecules ICAM-1 and VCAM-1 on the endothelium, and LFA-1, MAC-1, and VLA-4 on the leukocytes. Endotoxin infusion increased glomerular PMN and MO number in Pr, PSP, and DEC rats, all of which have elevated P levels, but not in C rats, which do not. The endotoxin-induced expression of adhesion molecules, associated with this influx of inflammatory cells, varied with the reproductive condition. In C rats there was no increased adhesion molecule expression after endotoxin treatment, in Pr rats there was increased expression of both the combinations ICAM-1/LFA-1 and VCAM-1/VLA-4. DEC rats did not express either of these combinations (although there was expression of ICAM-1); PSP rats expressed the combination ICAM-1/MAC-1. Adhesion molecule expression thus seems to be regulated by ovarian (e.g., P) and placental factors (e.g., of trophoblastic and decidual origin). Because the different combinations of adhesion molecules in the various reproductive conditions after exposure to endotoxin led to more or less the same leukocyte influx under these conditions, the increased sensitivity to endotoxin of pregnant individuals cannot be reduced to differences in leukocyte influx into the glomeruli.

Animals↗
PubMed1997

Modulation of glomerular ECTO-ADPase expression by oestradiol. A histochemical study.

The effect of 17-beta-oestradiol (OE2) upon the activity of the glomerular anti-thrombotic ecto-enzyme ADPase was studied in cyclic and ovariectomized (OVX) Wistar rats. On day 0 (i.e. at the time of ovariectomy or 11 days after ovariectomy) rats received OE2-releasing Silastic implants or empty implants and were sacrificed on day 3, 10 or 21. Cryostat kidney sections were histochemically stained for ecto-ADPase activity using enzyme-histochemistry and glomerular reaction product was quantitatively evaluated by computerized image analysis. Both the histological distribution of reaction product in each glomerulus, as reflected by the relative glomerular area covered with reaction product, as well as enzyme activity, as reflected by staining intensity of the reaction product, were scored. The results show significantly decreased histological distribution after OVX; OVX, however, did not change enzyme activity. It further appeared that OE2 (partly) prevented the decrease of histological distribution in OVX rats, while the enzyme activity was significantly increased by exogenous OE2. In cyclic rats, OE2 did not change histological distribution, although OE2 significantly increased enzyme activity in these rats. It is concluded that glomerular ecto-ADPase expression in the rat kidney is influenced by one or more ovarian factor(s), a very likely candidate being oestradiol. These results may thus point to a dual action of OE2 upon haemostasis: In addition to the known enhancement of procoagulatory plasma factors by OE2, also anti-aggregatory effects may be stimulated by OE2 as reflected by upregulation of vessel wall associated ecto-ADPase activity.

Analysis of Variance↗
PubMed1996

Role of gonadotrophin releasing hormone baseline concentrations in the control of pituitary gonadotrophin and ovarian steroid secretion in the pseudopregnant rat.

To study the effect of moderately elevated gonadotrophin releasing hormone (GnRH) baseline concentrations during the luteal and the follicular phase, pseudopregnant rats were infused s.c. with GnRH at several doses for 5 days. These rats were also treated with oestradiol or sham-treated during the last 3 days of GnRH treatment. GnRH infusions started on day 7 or day 3 of the luteal phase of the ovulatory cycle; in the rat, the luteal phase or pseudopregnancy lasts about 10 days. Luteinizing hormone (LH) and follicle stimulating hormone (FSH) responses were induced by i.v. injection of GnRH on days 12 (after expected luteolysis) or on day 8 (before expected luteolysis). In normal rats the LH and FSH responses induced by GnRH on day 12 were higher than on day 8 (approximately 160 and approximately 50% respectively). In GnRH-infused rats the LH and FSH responses were not increased. In these rats the luteal phase was extended (the plasma progesterone concentrations remained high) and the onset of the follicular phase was postponed (plasma oestrogen concentrations did not increase). Oestradiol increased the day 12 LH and FSH responses; this effect of oestradiol was suppressed by GnRH infusion. On day 8, exogenous oestradiol also increased the LH and FSH responses, but again the effect of oestradiol was suppressed when the animals were concomitantly infused with GnRH. These data may suggest that in the rat, GnRH baseline concentrations participate in the neuroendocrine system controlling gonadotrophin secretion and hence the ovulatory cycle.

Animals↗
PubMed1996

The glomerular filtration rate during pregnancy: saline infusion enhances the glomerular filtration rate in the pregnant rat.

The glomerular filtration rate (GFR) of pregnant rats is generally believed to exceed non-pregnant values. This notion is primarily based upon standard insulin clearances. However, the insulin clearance requires continuous infusion of insulin usually dissolved in saline. Since saline infusion per se in pregnancy may influence the GFR, in the present study the effect of saline infusion upon the GFR in pregnant as compared with cyclic rats was investigated using various methods. The standard insulin clearance was compared using the standard 51Cr-EDTA method which does not require saline infusion. Clearance of insulin dissolved in glucose (5% in distilled water) instead of saline was also tested, while the 51Cr-EDTA method was employed using additional fluid infusion with either saline or 5% glucose in distilled water in an identical manner as compared with the insulin method. The GFR was also studied in conscious rats using 51Cr-EDTA clearance with and without fluid infusion. The distribution volume of 51Cr-EDTA was measured in nephrectomized rats (pregnant and cyclic) with and without saline or glucose infusions. The results show a significant increase of the GFR in pregnant rats as compared with cyclic rats only when saline was infused during the measurement; thus, GFR measurements without fluid infusion or replacement of saline by glucose during the measurements did not show a significant increase of GFR in pregnant rats. The volume of distribution per gram body weight of 51Cr-EDTA after saline infusion, but not after glucose infusion, was significantly increased as compared with the values obtained without additional infusion. It is concluded that the increase of the GFR seen in pregnant rats when either the 51Cr-EDTA method or the insulin method is accompanied by saline loading is rather due to infusion of saline in the pregnant animal and not a result of the pregnant condition per se.

Animals↗
PubMed1995

Lack of evidence for dopamine autoreceptors in the mediobasal hypothalamus: a microdialysis study in awake rats.

To determine the functional presence of dopamine (DA) autoreceptors on tuberoinfundibular dopamine (TIDA)-ergic neurons in awake rats, a microdialysis probe was implanted into the mediobasal hypothalamus (MBH). In the presence of the re-uptake inhibitor nomifensine, which increased DA levels to 350% of basal values, systemic administration of the non-selective D1/D2 antagonist haloperiol induced an immediate increase in DA and DOPAC levels to 145% of pretreatment values. However, neither local infusion of the selective D2 antagonist sulpiride nor of the D1 antagonist SCH 23390 affected the nomifensine-elevated extracellular DA or DOPAC levels in the MBH. Systemic administration of the D2 antagonist raclopride equally did not affect the nomifensine-elevated DA release in the MBH. Upon basal extracellular DA levels (without nomifensine), local infusion of the D2 agonist (-)N-0437 equally did not affect the DA or DOPAC levels in the MBH. Furthermore, the increase in DA levels induced by haloperidol could not be antagonized by the D1 agonist CY 208-243. Therefore, the present study does not provide support for the concept of functional autoreceptors located on TIDA neurons regulating the release of DA. Possibly, the effect of haloperidol was non-DA-ergic in character.

3,4-Dihydroxyphenylacetic Acid↗