Endothelium and aortic contraction to endothelin-1 in the pregnant rat

2000 ◽  
Vol 78 (5) ◽  
pp. 372-377 ◽  
Author(s):  
Amadou Moctar Dièye ◽  
Alexis Gairard
Keyword(s):  
Receptor Antagonist ◽  
Late Pregnancy ◽  
Female Rats ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Endothelin 1 ◽  
Key Words Endothelin ◽  
Vasoconstrictor Peptide ◽  
Aortic Contraction

Endothelium-derived factors modulate tone and may be involved in hyporeactivity to vasoconstrictors, such as norepinephrine or angiotensin II, as has been previously described during gestation. The endothelium produces endothelin-1, a major vasoconstrictor peptide, therefore aortic contractions to endothelin-1 (10-10 to 3 ×10-7 M) were used to assess the role of the endothelium in pregnant Wistar rats (at 20 days of gestation). Late pregnancy is characterized by a significantly diminished systolic blood pressure in conscious rats (-17 mmHg, P < 0.001, n = 14). In pregnant and in age-matched nonpregnant female rats, endothelin-1 induced aortic contraction was greater when endothelium was present (at least P < 0.01). Indomethacin significantly reduced this contraction in aortic rings with intact endothelium in all groups. In aortic rings that had endothelium physically removed, contraction to endothelin-1 was greater in pregnant rats than in nonpregnant ones. Indomethacin decreased contraction of aortic rings in pregnant rats only. These results suggest an enhanced synthesis of vasoconstrictors by cyclooxygenases in vascular smooth muscle during pregnancy. In vessels with intact endothelium, we did not find hyporeactivity to endothelin-1 during late pregnancy. Contraction to endothelin-1 involved ETA receptors because it was decreased by BQ-123, an ETA receptor antagonist, whereas there was no significant change when using BQ-788, an ETB receptor antagonist. Key words: endothelin-1, endothelium, contraction, aorta, gestation.

PLASMA PROLACTIN AND PROGESTERONE RESPONSES TO MATING ARE ALTERED IN AGED RATS

1981 ◽  
Vol 90 (2) ◽  
pp. 179-191 ◽  
Author(s):  
S. HENDRICKS ◽  
C. A. BLAKE
Keyword(s):  
Plasma Concentrations ◽  
External Jugular Vein ◽  
Female Rats ◽  
Plasma Prolactin ◽  
Aged Rats ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Plasma Progesterone ◽  
The One ◽  
The Right

The effects of varying amounts of copulatory stimulation on patterns of plasma concentrations of prolactin and progesterone were evaluated in 3- and 12-month-old female rats. The 12-month-old group included rats which still exhibited oestrous cycles and rats in persistent vaginal oestrus (PVO). The extent of copulatory stimulation was defined by the number of intromissions received during mating: ≤5,15 or > 50. Blood samples were drawn over the 8 days after mating through a cannula inserted into the right external jugular vein. Plasma from the samples was assayed for prolactin and progesterone. In aged but still cyclic rats, pregnancy rates were positively correlated with the number of intromissions received during mating. Only one rat in PVO became pregnant. All animals which became pregnant and rats in PVO which, after mating, exhibited a disruption of the pattern of PVO, showed the nocturnal surge of plasma prolactin characteristic of pregnant and pseudopregnant rats. While these surges persisted until day 8 after mating in pregnant animals, they were absent by this time in the rats in PVO. Prolactin surges were present in some but not all of the aged rats which did not become pregnant. Progesterone concentrations were raised in all pregnant animals except the one pregnant rat in PVO and, while not related to the number of intromissions, concentrations were higher 8 days after mating in young compared with those in aged pregnant rats. Plasma progesterone was low in rats in PVO regardless of disruption of the pattern of PVO. We have concluded that the failure of limited copulatory stimulation to induce pregnancy in older rats results, at least in part, from its failure to initiate nocturnal prolactin surges. Nevertheless, our data suggest that matings which are not experimentally limited should provide ample stimulation to establish such surges. Although reduced plasma concentrations of prolactin and progesterone at pro-oestrus and reduced plasma progesterone through part of gestation may contribute to decreasing fertility in aged rats, other unidentified factors appear to be involved in mediating the capacity of extensive copulatory stimulation to induce pregnancy in these animals.

Regulation of renal CYP4A expression and 20-HETE synthesis by nitric oxide in pregnant rats

2003 ◽  
Vol 285 (2) ◽  
pp. F295-F302 ◽  
Author(s):  
Mong-Heng Wang ◽  
Jishi Wang ◽  
Hsin-Hsin Chang ◽  
Barbara A. Zand ◽  
Miao Jiang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Rat Kidney ◽  
Late Pregnancy ◽  
Inhibitory Effect ◽  
Female Rats ◽  
Male Rats ◽  
Pregnant Rats ◽  
Renal Vasoconstriction ◽  
Dependent Inhibition

20-Hydroxyeicosatetraenoic acid (20-HETE), which promotes renal vasoconstriction, is formed in the rat kidney primarily by cytochrome P-450 (CYP) 4A isoforms (4A1, 4A2, 4A3, 4A8). Nitric oxide (NO) has been shown to bind to the heme moiety of the CYP4A2 protein and to inhibit 20-HETE synthesis in renal arterioles of male rats. However, it is not known whether NO interacts with and affects the activity of CYP4A1 and CYP4A3, the major renal CYP4A isoforms in female rats. Incubation of recombinant CYP4A1 and 4A3 proteins with sodium nitroprusside (SNP) shifted the absorbance at 440 nm, indicating the formation of a ferric-nitrosyl-CYP4A complex. The absorbance for CYP4A3 was about twofold higher than that of CYP4A1. Incubation of SNP or peroxynitrite (PN; 0.01–1 mM) with CYP4A recombinant membranes caused a concentration-dependent inhibition of 20-HETE synthesis, with both chemicals having a greater inhibitory effect on CYP4A3-catalyzed activity. Moreover, incubation of CYP4A1 and 4A3 proteins with PN (1 mM) resulted in nitration of tyrosine residues in both proteins. In addition, PN and SNP inhibited 20-HETE synthesis in renal microvessels from female rats by 65 and 59%, respectively. We previously showed that microvessel CYP4A1/CYP4A3 expression and 20-HETE synthesis are decreased in late pregnancy. Therefore, we investigated whether such a decrease is dependent on NO, the synthesis of which has been shown to increase in late pregnancy. Administration of NG-nitro-l-arginine methyl ester (l-NAME) to pregnant rats for 6 days ( days 15- 20 of pregnancy) caused a significant increase in systolic blood pressure, which was prevented by concurrent treatment with the CYP4A inhibitor 1-aminobenzotriazole (ABT). Urinary NO2/NO3 excretion decreased by 40 and 52% in l-NAME- and l-NAME + ABT-treated groups, respectively. Interestingly, renal microvessel 20-HETE synthesis showed a marked increase following l-NAME treatment, and this increase was diminished with coadministration of ABT. These results demonstrate that NO interacts with CYP4A proteins in a distinct manner and it interferes with renal microvessel 20-HETE synthesis, which may play an important role in the regulation of blood pressure and renal function during pregnancy.

Resource sharing in rat gestation: role of maternal cardiovascular hemodynamics

1990 ◽  
Vol 258 (6) ◽  
pp. R1299-R1307 ◽  
Author(s):  
D. A. Blizard ◽  
T. G. Folk
Keyword(s):  
Resource Sharing ◽  
Peripheral Resistance ◽  
Positive Association ◽  
Late Pregnancy ◽  
Late Gestation ◽  
Alternative View ◽  
Pregnant Rat ◽  
Cardiovascular Hemodynamics ◽  
Laboratory Rat

There is a substantial decrease in blood pressure (BP) in late pregnancy in the laboratory rat. It is so pronounced that manipulations that produce sustained elevations in BP in nonpregnant animals have little or no effect during pregnancy. It is commonly believed that this decrease in BP is a consequence of a large decrease in total peripheral resistance resulting from the passive combination of the placental vasculature with a preexisting maternal vasodilation. An alternative view is presented here. We suggest that, in small mammals like the laboratory rat, pregnancy severely challenges the ability of the maternal cardiovascular system to meet its metabolic demands, so that during the last stages of maturation of the low-resistance placental circulation delivery of vital metabolic or nutritional substances to the maternal vasculature becomes marginal. When the so-called maternal hemodynamic preservation threshold is reached, a pronounced and wide-spread vasodilation occurs to maintain adequate perfusion of maternal organs. The late-gestational decrease in BP thus reflects a dynamic interaction between the maternal and placental circulations rather than reflecting their passive combination. The hypothesis provides a framework for the integrated discussion of a number of important phenomena: the fact that hypertensive rats exhibit a larger decrease in BP in late gestation than normotensive rats; the existence of a positive association between litter size and the magnitude of the late-gestational decrease in BP; and, finally, the well-established ability of the food-restricted pregnant rat to compartmentalize its nutritional resources.

Hyperlipemia and ketosis in the pregnant rat

1964 ◽  
Vol 206 (4) ◽  
pp. 796-804 ◽  
Author(s):  
Robert O. Scow ◽  
Sidney S. Chernick ◽  
Marlene S. Brinley
Keyword(s):  
Blood Glucose Concentration ◽  
Late Pregnancy ◽  
Maternal Blood ◽  
Insulin Administration ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Fat Mobilization ◽  
Fractional Clearance ◽  
Ad Libitum ◽  
Fasted Rats

Pregnant rats fasted on the 18th or 19th day of gestation developed hypoglycemia, severe ketosis, and hyperlipemia. The latter, which consisted primarily of triglycerides, was accompanied by increased plasma free fatty acids and accumulation of fat in the liver and kidneys. The effects of fasting were diminished by starting the fast earlier in pregnancy or by hysterectomy. Both ketosis and hyperlipemia were corrected by administration of insulin, tolbutamide, or glucose. The findings indicate that increased fat mobilization and ketosis in fasting pregnant rats are the result of insulin lack. It is suggested that the high priority of the fetuses for glucose reduced the maternal blood glucose concentration to a level too low to stimulate insulin secretion during fasting. Fasting did not alter the rapid growth of the fetuses. Pregnant rats fed ad libitum also developed hypertriglyceridemia if the diet contained fat. This hyperlipemia, unlike that in the fasted rats, was not due to increased fat mobilization and was unaffected by insulin administration. It is concluded that the fractional clearance of blood triglycerides is greatly reduced during late pregnancy.

scholarly journals Hormonal control of Luteal 20α-Hydroxy steroid dehydrogenase and Δ5-3β-hydroxy steroid dehydrogenase during luteolysis in the pregnant rat

1975 ◽  
Vol 152 (3) ◽  
pp. 433-443 ◽  
Author(s):  
R G Rodway ◽  
N J Kuhn
Keyword(s):  
Prostaglandin F2α ◽  
Late Pregnancy ◽  
Normal Pregnancy ◽  
Hormonal Control ◽  
Placental Lactogen ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Hydroxy Steroid ◽  
Steroid Dehydrogenase

Treatment of pregnant rats with human chorionic gonadotrophin, luteotrophin (luteinizing hormone), luteotrophin-releasing hormone, prostaglandin F2α, aminoglutethimide, or by foetoplacental removal or hysterectomy achieved a common multiple-response pattern, namely increased activity of luteal 20α-hydroxy steroid dehydrogenase with decreased activity of delta5-3β-hydroxy steriod dehydrogenase and release of delta4-3-oxo steroids in vitro. 2. Similar effects of foetoplacental removal are noted in pregnant mice. 3. Gonadotrophin induced lower activities of 20α-hydroxy steroid dehydrogenase, except at the very end of pregnancy, and partly inhibited the induction caused by foetoplacental removal. 4. The results suggest that existence of a placental factor that restrains these changes until the end of normal pregnancy, which is produced in amounts proportional to the number of placentae and is conveyed to the ovary via the blood. 5. This factor was not replaced by prolactin. 6. It is argued that neither placental lactogen nor pituitary luteotrophin participate in the induction of 20α-hydroxy steroid dehydrogenase at late pregnancy in the rat. 7. Aminoglutethimide induced 20α-hydroxy steroid dehydrogenase only in late pregnancy. This was partly reversed by progesterone, wholly reversed by progesterone plus oestrogen, and did not involve the pituitary.

The plasma pattern of growth hormone in conscious rats during late pregnancy

1990 ◽  
Vol 124 (2) ◽  
pp. 191-198 ◽  
Author(s):  
L. Carlsson ◽  
S. Edén ◽  
J.-O. Jansson
Keyword(s):  
Late Pregnancy ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Female Rats ◽  
Pregnant Rats ◽  
Fourfold Increase ◽  
Pregnant Females ◽  
Basal Plasma ◽  
Analysis Computer ◽  
Plasma Gh

ABSTRACT The plasma GH levels of female rats during late pregnancy were determined using an automatic method for repetitive blood sampling from conscious animals. The plasma GH patterns were analysed by a pulse analysis computer program (PULSAR). The mean plasma GH levels were about twofold higher in pregnant females on days 15, 18 and 22 of gestation than in age-matched non-pregnant females. The basal plasma GH levels were also increased, while there was no change in GH pulse amplitude or frequency. The augmentation of GH release was even more pronounced on day 20 of gestation, with a fourfold increase in mean plasma GH levels compared with those in non-pregnant females. This increase reflected an increase in both basal plasma GH levels and GH pulse amplitude, but there was no increase in pulse frequency. In female rats that delivered on day 22 of gestation, the basal and mean plasma GH levels increased during parturition. Pregnant females consistently responded to multiple i.v. infusions of 1 μg human GH-releasing factor analogue (hGRF(1–29)-NH2) given at 45-min intervals on day 18 of gestation. Both basal and GRF analogue-stimulated plasma GH levels were undetectable after hypophysectomy of pregnant rats. The present study demonstrates an increase in basal plasma GH levels during late pregnancy and a marked increase in both basal plasma GH levels and GH pulse amplitude on day 20 of gestation. Furthermore, hypophysectomy of pregnant rats results in undetectable GH levels, indicating that the high levels of GH during pregnancy are derived from the pituitary. Journal of Endocrinology (1990) 124, 191–198

EFFECTS OF INJECTIONS OF MONOAMINE OXIDASE INHIBITOR OR SALINE INTO THE UTERUS IN LATE PREGNANCY ON UTERINE CATECHOLAMINE LEVELS RELATED TO ABNORMAL PARTURITION IN RATS

1975 ◽  
Vol 67 (3) ◽  
pp. 371-383 ◽  
Author(s):  
J. P. MALTIER ◽  
F. CAVAILLE
Keyword(s):  
Monoamine Oxidase ◽  
Monoamine Oxidase Inhibitor ◽  
Late Pregnancy ◽  
Ringer Solution ◽  
Oxidase Inhibitor ◽  
Saline Injection ◽  
Mao Inhibitor ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Catecholamine Levels

SUMMARY Injection of a monoamine oxidase (MAO) inhibitor (nialamide) into the uterus of an anaesthetized and laparotomized rat on day 20 of pregnancy severely disturbed parturition. Injection of the solvent (0·9% isotonic NaCl solution) at the same stage of gestation produced the same but less frequent disturbances. When the rats were injected on days 19 or 21, impairment was less marked than on day 20. Therefore, day 20 seems to be a critical period for the onset of parturition. Injection of Ringer solution into the uterus on day 20 had effects analogous to those of saline injection at the same stage. Anaesthesia induced with ether, laparotomy of the pregnant rat on day 20, and handling of the uterine horns without injection of either Ringer or NaCl also disturbed parturition in 70% of the rats treated. Nevertheless, disorders were not as severe as those after injection. Laparotomy alone on day 20 did not disturb parturition. The effects on parturition of a saline injection into the uterus on day 20 were greatly decreased when the injection was performed on pregnant rats adrenalectomized on day 14, or on pregnant rats pretreated on days 18 and 19 with an agent blocking the adrenergic β receptors (propranolol); 70–80% of the treated rats had normal deliveries. In control rats, uterine catecholamine levels were markedly modified between days 21 and 22 of gestation. These changes did not occur in rats injected with MAO inhibitor or saline.

scholarly journals Intracerebroventricular administration of the prolactin (PRL) receptor antagonist, S179D PRL, disrupts parturition in rats

Reproduction ◽  
2007 ◽  
Vol 134 (1) ◽  
pp. 155-160 ◽  
Author(s):  
B C Nephew ◽  
J Amico ◽  
H M Cai ◽  
A M Walker ◽  
R S Bridges
Keyword(s):  
Receptor Antagonist ◽  
Plasma Concentrations ◽  
Female Rats ◽  
Plasma Progesterone ◽  
Blood Samples ◽  
Period Effects ◽  
Preliminary Study ◽  
Nulliparous Female ◽  
Plasma Prl

The prolactin (PRL) receptor antagonist S179D PRL delays the onset of maternal behavior in steroid-primed nulliparous female rats. The present study investigated the role of the neural PRL system in the process of parturition. A preliminary study indicated that S179D PRL treatments administered by ALZET minipump to the lateral ventricle severely disrupted parturition. To examine the likely causes of this disruption, a group of timed-pregnant catheterized rats was continuously infused with S-179D PRL (0.001 and 0.1 ng/h) or vehicle control to the lateral ventricles for 3 days (gestation days 21–23), and serial blood samples were taken throughout this period. Effects of the treatments on parturition were recorded, and blood samples were assayed for PRL, progesterone, and oxytocin. Significantly fewer S179D PRL-treated rats successfully delivered by 1500 h on day 23 of gestation when compared with controls. The higher dose of S179D PRL also significantly suppressed the prepartum rise in PRL throughout the prepartum period, while the lower dose only affected plasma PRL during the first 24 h of treatment. No significant effects of the antagonist on plasma progesterone or oxytocin were detected. We conclude that disruption of parturition by S179D PRL is not caused by significant alterations in the plasma concentrations of progesterone or oxytocin. S179D PRL may indirectly act on parturition through the modulation of prepartum PRL. These findings suggest a previously unrecognized role for PRL in the regulation of parturition.

scholarly journals Role of Insulin Receptor Substrate-1 Serine 307 Phosphorylation and Adiponectin in Adipose Tissue Insulin Resistance in Late Pregnancy

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 5933-5942 ◽  
Author(s):  
Julio Sevillano ◽  
Javier de Castro ◽  
Carlos Bocos ◽  
Emilio Herrera ◽  
M. Pilar Ramos
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Receptor ◽  
Tyrosine Phosphorylation ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Late Pregnancy ◽  
Serine Phosphorylation ◽  
Pregnant Rats

Insulin resistance is a hallmark of late pregnancy both in human and rat. Adipose tissue is one of the tissues that most actively contributes to this reduced insulin sensitivity. The aim of the present study was to characterize the molecular mechanisms of insulin resistance in adipose tissue at late pregnancy. To this end, we analyzed the insulin signaling cascade in lumbar adipose tissue of nonpregnant and pregnant (d 20) rats both under basal and insulin-stimulated conditions. We found that the levels of relevant signaling proteins, such as insulin receptor (IR), IR substrate-1 (IRS-1), phosphatidylinositol 3-kinase, 3-phosphoinositide-dependent kinase-1, ERK1/2, and phosphatase and tensin homolog (PTEN) did not change at late pregnancy. However, insulin-stimulated tyrosine phosphorylation of both IR and IRS-1 were significantly decreased, coincident with decreased IRS-1/p85 association and impaired phosphorylation of AKR mouse thymoma viral protooncogene (Akt) and ERK1/2. This impaired activation of IRS-1 occurred together with an increase of IRS-1 phosphorylation at serine 307 and a decrease in adiponectin levels. To corroborate the role of IRS-1 in adipose tissue insulin resistance during pregnancy, we treated pregnant rats with the antidiabetic drug englitazone. Englitazone improved glucose tolerance, and this pharmacological reversal of insulin resistance was paralleled by an increase of adiponectin levels in adipose tissue as well as by a reduction of IRS-1 serine phosphorylation. Furthermore, the impaired insulin-stimulated tyrosine phosphorylation of IRS-1 in adipose tissue of pregnant animals could be restored ex vivo by treating isolated adipocytes with adiponectin. Together, our findings support a role for adiponectin and serine phosphorylation of IRS-1 in the modulation of insulin resistance in adipose tissue at late pregnancy.

Transcriptomes reveal alterations in gravity impact circadian clocks and activate mechanotransduction pathways with adaptation through epigenetic change

2015 ◽  
Vol 47 (4) ◽  
pp. 113-128 ◽  
Author(s):  
Theresa Casey ◽  
Osman V. Patel ◽  
Karen Plaut
Keyword(s):  
Gene Expression ◽  
Late Pregnancy ◽  
Global Gene Expression ◽  
Circadian Clocks ◽  
Epigenetic Change ◽  
Pregnant Rats ◽  
Affymetrix Genechips ◽  
Expression Of Genes ◽  
The Impact

Few studies have investigated the impact of alterations in gravity on mammalian transcriptomes. Here, we describe the impact of spaceflight on mammary transcriptome of late pregnant rats and the effect of hypergravity exposure on mammary, liver, and adipose transcriptomes in late pregnancy and at the onset of lactation. RNA was isolated from mammary collected on pregnancy day 20 from rats exposed to spaceflight from days 11 to 20 of gestation. To measure the impact of hypergravity on mammary, liver, and adipose transcriptomes we isolated RNA from tissues collected on P20 and lactation day 1 from rats exposed to hypergravity beginning on pregnancy day 9. Gene expression was measured with Affymetrix GeneChips. Microarray analysis of variance revealed alterations in gravity affected the expression of genes that regulate circadian clocks and activate mechanotransduction pathways. Changes in these systems may explain global gene expression changes in immune response, metabolism, and cell proliferation. Expression of genes that modify chromatin structure and methylation was affected, suggesting adaptation to gravity alterations may proceed through epigenetic change. Altered gravity experiments offer insights into the role of forces omnipresent on Earth that shape genomes in heritable ways. Our study is the first to analyze the impact of alterations in gravity on transcriptomes of pregnant and lactating mammals. Findings provide insight into systems that sense gravity and the way in which they affect phenotype, as well as the possibility of sustaining life beyond Earth's orbit.

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