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M M Faas

Publications and source records attributed to M M Faas.

17 recordsLinked to original sources

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

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

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

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

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

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

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

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

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

Glomerular inflammation in pregnant rats after infusion of low dose endotoxin. An immunohistological study in experimental pre-eclampsia.

Increased endotoxin sensitivity during pregnancy occurs in many animals, including rats. The mechanism of this phenomenon is not understood. In the present study it was investigated whether this increased sensitivity is reflected by an altered inflammatory pattern. Inflammatory cell influx, the O2(-)-producing potential of these cells, and expression of adhesion molecules was studied in the glomeruli of pregnant and cyclic rats at various intervals after low dose endotoxin infusion. Kidney sections were stained for monocytes and adhesion molecules (ICAM-1, VCAM-1, LFA-1, and VLA-4) using monoclonals, while potentially O2(-)-producing neutrophils (ie, activated neutrophils) were quantified using immunohistochemical methods. The results show early glomerular influx of activated neutrophils, maximally 4 hours after endotoxin. Both absolute neutrophil counts and relative numbers of activated neutrophils were significantly increased in pregnant versus cyclic rats. In contrast to cyclic rats, showing transient monocyte influx, in pregnant endotoxin-treated rats monocyte influx reaches a maximum at t = 168 hours. These cell kinetics were paralleled by expression of the various adhesion molecules. It was concluded that pregnancy profoundly influences not only the inflammation kinetics after endotoxin, but also the violence of the reaction, reflected by activated neutrophils. This altered glomerular inflammatory pattern may help to explain why low dose endotoxin infusion induces pre-eclamptic-like symptoms (such as an intraglomerular prothrombotic microenvironment and proteinuria) exclusively in the pregnant rat.

Animals

A new animal model for human preeclampsia: ultra-low-dose endotoxin infusion in pregnant rats.

OBJECTIVE: An animal model for preeclampsia was developed by means of an ultra-low-dose endotoxin infusion protocol in conscious pregnant rats. STUDY DESIGN: Rats received a permanent jugular vein cannula on day 0 of pregnancy, through which endotoxin (1.0 micrograms/kg body weight) (n = 10) or saline solution (n = 6) was infused during 1 hour on day 14 of pregnancy. Blood pressure, albuminuria, and platelet counts were measured, and histopathologic studies was performed in these rats. RESULTS: A significant increase of blood pressure (p < 0.05) and of urinary albumin excretion (p < 0.05) was observed in endotoxin-treated pregnant animals, in contrast to control pregnant rats receiving saline solution. Platelet coagulopathy was found and glomerular fibrinogen deposits could be detected only in the endotoxin-treated pregnant rats. In addition, the activity of the glomerular antithrombotic enzyme adenosine diphosphatase was decreased in endotoxin-treated pregnant rats compared with saline solution-treated pregnant rats. CONCLUSION: Because histopathologic and clinical events in this model mimic predominant features of human preeclampsia, this model may enable further study into the pathophysiologic mechanisms of this complication of pregnancy.

Albuminuria

Reproductive condition, glomerular adenosine diphosphatase activity, and platelet aggregation in the rat: effect of endotoxin.

In experiment A, the activity of the glomerular antithrombotic enzyme adenosine diphosphatase (ADPase) and the sensitivity of this enzyme for endotoxin (1.0 microgram/kg BW) in various reproductive conditions of female rats were studied through use of enzyme histochemical methods. In experiment B, the effect of this dose of endotoxin on the thrombotic tendency of the glomeruli in pregnant (Pr) and pseudopregnant (PSP) rats was studied by means of ex vivo alternate perfusion of the kidneys with human platelets and adenosine diphosphate (ADP). In experiment A, cyclic (C), ovariectomized (OVX), Pr, and PSP rats were infused with endotoxin or saline. Three days later (for Pr and PSP rats, Day 8), animals were killed. In intact rats (C, Pr, PSP), the activity of glomerular ADPase was the same; however, the activity decreased after OVX. Endotoxin decreased the activity of glomerular ADPase in Pr rats only. In endotoxin-treated Pr rats, spontaneously formed platelet microaggregates were present in a few glomeruli; in glomeruli of the other groups, microaggregates were not observed. Platelet microaggregates were also present in the venous microvasculature of endotoxin-treated Pr rats and, to a lesser extent, in that of other groups, while saline-treated OVX rats were negative in this respect. In experiment B, Pr and PSP rats were treated as in experiment A; ex vivo kidney perfusion was performed on Day 8. Immediately after perfusion, rats were killed. Only Pr endotoxin-treated rats exhibited significantly increased intraglomerular platelet aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate

Regulation of peripheral glucagon concentrations in cyclic, pregnant, and lactating rats.

In the rat, peripheral glucagon concentrations were studied throughout pregnancy and lactation. Basal glucose concentrations were decreased during late pregnancy and during lactation, but basal glucagon concentrations were not affected. Infusion of glucose (7.4 mg/min) caused an elevation of the glucose concentrations, which became lower in the course of lactation, and a suppression of the glucagon concentrations which was the same throughout pregnancy and lactation. Ingestion of 336 mg of glucose or 1 g of rat chow throughout pregnancy and lactation induced a transient increase of the glucose concentrations and a biphasic glucagon response: following a short-lasting elevation, the glucagon concentrations became suppressed. The glucagon responses to these tests did not change during pregnancy and lactation. It is concluded that the regulation of the peripheral glucagon concentration is not affected by pregnancy or lactation, and that the response of the glucagon concentration to a metabolic challenge varies with the kind of test (oral or intravenous) used.

Animal Nutritional Physiological Phenomena

The increased endotoxin-sensitivity of pregnant rats, as reflected by glomerular ecto-ADP-ase activity, is not dependent on the presence of decidual cells.

In the present study the possible role of decidual cells in the pregnancy-associated increased sensitivity of glomerular ecto-ADP-ase to endotoxin was investigated. Early (day 5) pregnant (E-Pr; n = 10), pseudopregnant (E-PSP; n = 10), (day 5), pseudopregnant rats with a decidualized uterus (E-DEC; n - 10), as well as late (day 14) pregnant (L-Pr; n = 10), pseudopregnant (L-PSP: n = 10) (day 14), and pseudopregnant rats with a decidualized uterus (E-DEC; n = 10) were infused with either endotoxin (1.0 mg/kg bw) or saline. Three days later rats were killed and specimens of the left kidney were snap-frozen. Cryostat kidney sections (4 microns) were stained for ecto-ADP-ase activity and quantitatively evaluated. The results show that only glomerular ecto-ADP-ase activity of both groups of pregnant rats (E-Pr and L-Pr) was significantly decreased after endotoxin infusion as compared to saline infusion. In the other groups of rats, no significant differences in ecto-ADP-ase activity were observed between saline and endotoxin infusion. It is concluded that decidual cells do not play a role in the increased sensitivity of ecto-ADP-ase to endotoxin during pregnancy.

Analysis of Variance