scholarly journals Lack of nitric oxide bioavailability in early pregnancy predisposes to dyslipidemia and surges preeclampsia and fetal growth retardation

2021 ◽  
Author(s):  
Aida A. Korish
Keyword(s):  
Nitric Oxide ◽  
Lipid Profile ◽  
Pregnancy Outcome ◽  
Normal Pregnancy ◽  
High Density Lipoproteins ◽  
No Production ◽  
Blood Lipid Profile ◽  
Pregnant Rats ◽  
Nitric Oxide Synthase Inhibitor ◽  
Poor Pregnancy Outcome

Background: Hyperlipidemia has been reported in preeclampsia (PrE) and is linked to poor pregnancy outcome and long-term cardiovascular complications. This study aimed to elucidate the relationship between nitric oxide (NO) and blood lipids levels during normal pregnancy and in NG-nitro-l-arginine methyl ester (L-NAME) - induced preeclampsia before and after magnesium sulphate (MgSO4) therapy and its effect on the pregnancy outcome.Methods: Forty female Wistar rats were divided into four groups: non pregnant (NP) group - non pregnant healthy rats receiving no treatment, control pregnant (Con-P) group - control pregnant rats receiving no treatment, pregnant (PE) group - pregnant animals with untreated PrE, and the pregnant MgSO4 (PE-Mg) group - pregnant animals with PrE- treated with MgSO4. The nitric oxide synthase inhibitor L-NAME was used to induce experimental model of PrE in the PE and the PE-Mg groups. The changes in total NO production, total cholesterol (TC), triglycerides (TG), low density lipoproteins (LDL-C), high density lipoproteins (HDL), LDL-C/HDL-C ratio, soluble vascular endothelial growth factor receptor-1 (sVEGFR1) also known as sFlt-1, blood pressure, kidney functions, body weight, and pregnancy outcome were assessed.Results: Decreased NO production in the PE group was associated with elevated TC, TG, LDL-C/HDL-C ratio, hypertension, proteinuria, increased urea, creatinine, and sFlt-1 levels, and poor pregnancy outcome demonstrated by high pup mortality rate and low birth weight. Increased NO production in the PE-Mg group treated with MgSO4 therapy was associated with decreased signs of preeclampsia and hypolipidemia and increased pup viability and birth weight.Conclusions: NO bioavailability is crucial for the homeostasis of the lipid profile in normal pregnancy and the prevention of preeclampsia. Routine periodic assessments of the blood lipid profile and the NO production in the pregnant females may be a helpful tool in early prediction of preeclampsia.

Evaluation of Low-dose Endotoxin Administration during Pregnancy as a Model of Preeclampsia

2000 ◽  
Vol 93 (6) ◽  
pp. 1446-1455 ◽  
Author(s):  
Yasser Sakawi ◽  
Margaret Tarpey ◽  
Yiu Fai Chen ◽  
David A. Calhoun ◽  
Michael G. Connor ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Low Dose ◽  
No Production ◽  
Pregnant Rats ◽  
Nitric Oxide Synthase Inhibitor ◽  
Endotoxin Administration ◽  
Before And After ◽  
Synthase Inhibitor ◽  
Plasma Nitrite ◽  
Oxide Synthase

Background Recent evidence implicates nitric oxide (*NO) in the pathogenesis of preeclampsia. The authors tested the hypothesis that administration of low-dose endotoxin to pregnant rats mimics the signs of preeclampsia in humans and that *NO and *NO-derived species play a role in that animal model. Methods Endotoxin was infused at doses of 1, 2 and 10 microg/kg over 1 h to rats on day 14 of pregnancy. Mean arterial pressure, urinary protein, urinary and plasma nitrite plus nitrate (NO2- + NO3-) concentrations, and platelet count were measured before and after the endotoxin infusion. In another group of pregnant rats, the nitric oxide synthase inhibitor L-nitroarginine methyl ester (L-NAME) was administered in drinking water at a dose of 3 mg x kg(-1) x d(-1) starting on day 7 of pregnancy. Endotoxin was then infused at 10 microg/kg on day 14 of pregnancy. Kidneys and uteroplacental units were examined histologically and analyzed immunohistochemically for 3-nitrotyrosine. Results Endotoxin administration at doses of 2 and 10 microg/kg caused proteinuria and thrombocytopenia in pregnant rats, but did not result in hypertension. Urinary NO2- + NO3- concentration, reflective of tissue *NO production rates, was significantly elevated in pregnant rats that received endotoxin at 10 microg/kg. Ingestion of L-NAME caused hypertension. Tissues from pregnant rats treated with L-NAME, endotoxin at 10 microg/kg, and a combination of L-NAME and endotoxin had increased 3-nitrotyrosine immunoreactivity. Conclusion Nitric oxide either directly or through secondary species plays a significant role in the biochemical and physiologic changes that occur in a rodent model of endotoxin-induced injury.

Apoptosis caused by an inhibitor of NO production in the decidua of rat from mid-gestation

2010 ◽  
Vol 235 (4) ◽  
pp. 455-462 ◽  
Author(s):  
Takehito Suzuki ◽  
Chiaki Nagamatsu ◽  
Takahiro Kushima ◽  
Ryu Miyakoshi ◽  
Kazuaki Tanaka ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Enzyme Activity ◽  
Caspase 3 ◽  
Control Group ◽  
Caspase 8 ◽  
No Production ◽  
Pregnant Rats ◽  
Nitric Oxide Synthase Inhibitor ◽  
Pregnant Rat ◽  
Synthase Inhibitor

We previously reported that nitric oxide (NO) is first detected in the uterus of a pregnant rat on gestational day 13.5 (GD13.5) and that NO levels peak on GD17.5. In addition, NO production in the uterus is mainly derived from the decidua and not the myometrium. The aim of the present study was to reveal the role of NO that peaked on GD17.5 of gestation in the decidua. To inhibit NO production, pregnant rats were continuously administered by an nitric oxide synthase inhibitor, NG-nitro-l-arginine-methyl ester (l-NAME) for 48 h. In the control group, saline was infused instead of l-NAME. After treatment, the decidua were obtained from GD13.5, GD17.5 and GD21.5 rats. Apoptosis and activated caspase-3-positive cells were observed by transferase-mediated dUTP nick-end labeling (TUNEL) assay and immunohistochemistry, respectively. The caspase-3 enzyme activity was also measured in the cell lysate from the decidua. The numbers of TUNEL-positive cells and activated caspase-3-positive cells each increased and the amount of caspase-3 activity also increased significantly in rats on GD17.5 than in rats in the control group, but no changes were observed in rats on GD13.5 and GD21.5. Furthermore, enzyme activity regarding the initiator caspases, caspase-8 and -9, upstream factors for caspase-3 in the caspase cascade, was measured simultaneously on GD17.5 under the same treatment. Caspase-8 and -9 enzyme activities increased significantly in the control group; an increment of caspase-8 activity was especially prominent. The present results indicate that an inhibitor of NO production caused apoptosis through typical apoptotic signals in the decidua on GD17.5, suggesting that an NO peak in the decidua is essential to cell survival and the maintenance of uterine formation.

Expression of nitric oxide synthase isoforms and detection of nitric oxide in rat placenta

2002 ◽  
Vol 282 (4) ◽  
pp. C762-C767 ◽  
Author(s):  
Tatsuya Takizawa ◽  
Hiroshi Yoshikawa ◽  
Miho Yamada ◽  
Hidetoshi Morita
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Pcr Analysis ◽  
No Production ◽  
Epr Spectrum ◽  
Pregnant Rats ◽  
Paramagnetic Resonance ◽  
Triplet Signal ◽  
Oxide Synthase ◽  
Nos Isoforms

Nitric oxide (NO) production in the rat placenta was monitored and quantified by electron paramagnetic resonance (EPR) spectroscopy with hemoglobin and an Fe- N-(dithiocarboxy)sarcosine (DTCS) complex as NO-trapping reagents. Expression of nitric oxide synthase (NOS) isoforms was also examined by quantitative RT-PCR analysis. The EPR spectrum of the placenta with hemoglobin trapping showed a three-line hyperfine structure ( g = 2.008 and a = 1.66-mT). The EPR signal was diminished after the placenta was homogenized or the NOS inhibitor l-NAME was administered to pregnant rats. Therefore, the specific signal was definitely identified as being derived from endogenous NO spin-trapped by hemoglobin, and the EPR spectrum showed that the NO adduct existed as a pentacoordinate α-NO heme species. The EPR spectrum of the placenta with Fe-DTCS trapping showed a triplet signal ( g = 2.038) derived from an NO-Fe-DTCS complex. The height of the triplet signal did not vary significantly with gestational stage during the last few days of gestation. At the gestational stages examined, the level of NOS II mRNA expression was significantly higher than that of NOS III mRNA. NOS II expression in term ( day 21.5) placenta was significantly increased compared with that in preterm ( day 19.5) placenta ( P < 0.01, n = 4 or 5). These results suggest that NOS II is the predominant producer of NO in the placenta and that NOS II-generated NO plays significant roles in the maintenance of placental functions immediately before birth.

Role of nitric oxide in the natriuretic and diuretic responses in pregnant rats

2003 ◽  
Vol 285 (5) ◽  
pp. F938-F944 ◽  
Author(s):  
Ali A. Khraibi ◽  
Tianzheng Yu ◽  
Daiyi Tang
Keyword(s):  
Nitric Oxide ◽  
Control Period ◽  
Fractional Excretion ◽  
Normal Pregnancy ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Sd Rats ◽  
Fractional Excretion Of Sodium ◽  
Lower Ability

Normal pregnancy is characterized by sodium conservation and increase in plasma volume, yet the natriuretic response to acute saline volume expansion (VE) is intact in pregnant rats. Nitric oxide (NO) has been suggested to play a role in renal and cardiovascular adaptations to normal pregnancy. The objective of this study was to determine the role of NO in the natriuretic and diuretic responses to VE during pregnancy. Infusion of NG-monomethyl-l-arginine (l-NMMA) was used to inhibit NO synthesis. Nine groups of Sprague-Dawley (SD) rats were studied: nonpregnant (NP-VE, n = 7), midterm pregnant (MP-VE, n = 8), and late-term pregnant (LP-VE, n = 7) SD groups that underwent VE alone after a control period; NP-l-NMMA ( n = 7), MP-l-NMMA ( n = 8), and LP-l-NMMA ( n = 7) SD groups that were infused with l-NMMA after a control period; and another three groups of SD rats (NP-VE-l-NMMA, n = 8; MP-VE-l-NMMA, n = 7; and LP-VE-l-NMMA, n = 12) that underwent simultaneous VE and l-NMMA infusion after a control period. The change in fractional excretion of sodium was 7.22 ± 1.03% for NPVE, 9.89 ± 1.85% for NP-l-NMMA, and 17.66 ± 1.85% for NP-VE-l-NMMA ( P < 0.05 vs. NP-VE and NP-l-NMMA); 6.61 ± 1.07% for MP-VE, 7.99 ± 1.92% for MP-l-NMMA, and 10.24 ± 1.91% for MP-VE-l-NMMA [not significant (NS) vs. MP-VE and MP-l-NMMA]; 8.20 ± 1.92% for LP-VE, 8.09 ± 0.70% for LP-l-NMMA, and 7.57 ± 1.11% for LP-VE-l-NMMA (both NS vs. LP-VE and LP-l-NMMA). The increase in renal interstitial hydrostatic pressure was significantly greater in all NP compared with pregnant groups with similar experimental intervention (i.e., VE, l-NMMA, or VE-l-NMMA). In conclusion, the natriuretic and diuretic responses to VE and l-NMMA infusion were additive in NP but not in pregnant rats, indicating a possible lower ability of pregnant rats to respond to combined significant natriuretic and diuretic stimuli.

Abstract 273: Increased Blood Pressure and Proteinuria and Absence of Increased Nitric Oxide (NO) Production During Pregnancy in the Dahl Salt Sensitive (S) Rat

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Ellen E Gillis ◽  
Jennifer N Mooney ◽  
Jan M Williams ◽  
Michael R Garrett ◽  
Jennifer M Sasser
Keyword(s):  
Blood Pressure ◽  
Genetic Model ◽  
Late Pregnancy ◽  
Normal Pregnancy ◽  
Kidney Cortex ◽  
No Production ◽  
Pregnant Rats ◽  
Telemetry Unit ◽  
Nos Inhibitor ◽  
Volume Retention

In normal pregnancy, systemic vasodilation due to increased NO production allows a drop in blood pressure (BP) despite increased volume retention. Little is known about the pathogenesis of preeclampsia, defined by increased BP and proteinuria, due to a lack of animal models that spontaneously develop the disease. Here we tested the hypothesis that the Dahl S rat, a genetic model of hypertension and kidney disease, is also a spontaneous model of preeclampsia. Female Dahl S rats were implanted with a telemetry unit, and baseline BP was recorded. Rats were placed in metabolic cages for 24 hr urine collection while on a low nitrate diet, and urinary protein and NO metabolite concentrations were measured via Bradford and Greiss assays, respectively. There were no differences in baseline BP (152±1 vs 151±4 mmHg) or proteinuria (61±10 vs 60±17 mg/d) in the rats selected for mating vs virgin rats (n=5-7). Pregnancy was confirmed by presence of sperm (day 1). Measurements were made during mid and late pregnancy (days 10-11, 17-18), and terminal measurements were taken on day 19. Pregnant rats exhibited an increase in BP and proteinuria with no change in urinary NOx excretion (Table), while no changes were observed in age-matched virgin rats. Kidney cortex abundance of neither NOS1 nor NOS3 was increased at late pregnancy; however, plasma concentration of the endogenous NOS inhibitor ADMA was increased in late pregnant compared to virgin rats (0.82±0.06 vs. 0.62±0.06 μM, p<0.05). These data suggest that the Dahl S rat cannot upregulate NO production during pregnancy; therefore, this relative NO deficiency may contribute to worsening hypertension and proteinuria during pregnancy in this strain.

Upregulation of endothelial and neuronal constitutive nitric oxide synthase in pregnant rats

1996 ◽  
Vol 271 (6) ◽  
pp. R1739-R1745 ◽  
Author(s):  
D. L. Xu ◽  
P. Y. Martin ◽  
J. St John ◽  
P. Tsai ◽  
S. N. Summer ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Western Blot ◽  
Mesenteric Arteries ◽  
No Production ◽  
Pregnant Rats ◽  
Neuronal Nos ◽  
Peripheral Arterial ◽  
Constitutive Nitric Oxide Synthase ◽  
Oxide Synthase ◽  
Nos Isoforms

Pregnancy is characterized by hemodynamic and body fluid alterations. Increased nitric oxide (NO) production has been suggested to play a role in the hemodynamic alterations of pregnancy and has also been reported to increase arginine vasopressin (AVP) release. We therefore hypothesized that gestation could increase both NO synthase (NOS) constitutive isoforms, neuronal NOS and endothelial NOS, and thereby contribute to the hyposmolality and peripheral arterial vasodilation of pregnancy, respectively. The present study was therefore undertaken to examine the constitutive NOS isoforms in aortas, mesenteric arteries, and hypothalami of pregnant rats on day 20 of gestation compared with age-matched nonpregnant rats. Plasma AVP was determined by radioimmunoassay and hypothalamic mRNA AVP by solution hybridization assay. Hypothalamic neuronal NOS was assessed by Northern blot and Western blot; endothelial NOS was assessed by Western blot in arteries and hypothalamus. The results demonstrated that 1) plasma AVP and hypothalamic AVP mRNA are increased in pregnant rats (n = 8), 2) neuronal NOS protein and mRNA are increased in hypothalamus of pregnant rats (n = 4), and 3) endothelial NOS expression, as assessed by Western blot analysis, is increased in both conductance (aorta) as well as resistance (mesenteric) arteries of pregnant rats (n = 4). We conclude that both of the constitutive NOS isoforms are increased in pregnant rats, suggesting that the peripheral arterial vasodilation and hyposmolality of pregnancy could be mediated by these isoforms.

Chronic hypoxia opposes pregnancy-induced increase in uterine artery vasodilator response to flow

2003 ◽  
Vol 284 (3) ◽  
pp. H820-H829 ◽  
Author(s):  
Stephanie Mateev ◽  
A. Hugo Sillau ◽  
Rhonda Mouser ◽  
Robert E. McCullough ◽  
Margueritte M. White ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Uterine Artery ◽  
Chronic Hypoxia ◽  
Normal Pregnancy ◽  
Nitric Oxide Synthase Inhibitor ◽  
Dimensional Changes ◽  
Vasodilator Response ◽  
Synthase Inhibitor ◽  
Oxide Synthase

We tested the hypotheses that pregnancy increases the uterine artery (UA) vasodilator response to flow and that this increase is impaired under conditions of chronic hypoxia (30 days, simulated elevation 3,960 m). UA were isolated from 24 normoxic or chronically hypoxic midpregnant guinea pigs and studied with the use of pressure myography. Normoxic pregnancy increased UA flow vasodilator response and protected against a rise in wall shear stress (WSS). Chronic hypoxia opposed these effects, prompting vasoconstriction at high flow and increasing WSS above levels seen in normoxic pregnant UA. The nitric oxide synthase inhibitor N G-nitro-l-arginine (l-NNA) eliminated the pregnancy-associated increase in flow vasodilation in normoxic UA, suggesting that increased nitric oxide production was responsible. The considerable residual vasodilation after nitric oxide synthase and cyclooxygenase inhibition implicated endothelial-derived hyperpolarizing factor (EDHF) as an additional contributor to flow vasodilation.l-NNA increased flow vasodilation in UA from chronically hypoxic animals, suggesting that chronic hypoxia may have lowered EDHF or elevated peroxynitrite production. In conclusion, flow is an important physiological vasodilator for the acute and more chronic UA dimensional changes required to increase uteroplacental blood flow during normal pregnancy. Chronic hypoxia may be a mechanism that opposes the pregnancy-associated rise in UA flow vasodilation, thereby increasing the incidence of preeclampsia and intrauterine growth restriction at a high altitude.

scholarly journals Renal nitric oxide production in rat pregnancy: role of constitutive nitric oxide synthases

2010 ◽  
Vol 299 (4) ◽  
pp. F830-F836 ◽  
Author(s):  
Cheryl A. Smith ◽  
Beth Santymire ◽  
Aaron Erdely ◽  
Vasuki Venkat ◽  
György Losonczy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Renal Cortex ◽  
Soluble Fraction ◽  
Splice Variants ◽  
Normal Pregnancy ◽  
No Production ◽  
Protein Abundance ◽  
Functional Studies ◽  
Enos Protein

Functional studies show that increased renal nitric oxide (NO) mediates the renal vasodilation and increased glomerular filtration rate that occur during normal pregnancy. We investigated whether changes in the constitutive NO synthases (NOS), endothelial (eNOS) and neuronal (nNOS), were associated with the increased renal NO production in normal midterm pregnancy in the rat. In kidneys from midterm pregnant (MP: 11–13 days gestation), late-term pregnant (LP: 18–20 days gestation), and similarly aged virgin (V) rats, transcript and protein abundance for eNOS and the nNOSα and nNOSβ splice variants, as well as the rate of l-arginine-to-l-citrulline conversion, were determined as a measure of NOS activity. At MP, renal cortical abundance of the total eNOS protein and phosphorylated (Ser1177) eNOS was reduced, and l-arginine-to-l-citrulline conversion in the cortical membrane fraction was decreased; these declines were also seen in LP. There were no changes in the eNOS transcript. In contrast, l-arginine-to-l-citrulline conversion in the soluble fraction of renal cortex increased at MP and then declined at LP. This MP increase was ablated by S-methylthiocitrulline, a nNOS inhibitor. Using Western blotting, we did not detect a change in the protein abundance or transcript of the 160-kDa nNOSα, but protein abundance and transcript of the nNOSβ were increased at MP in cortex. Collectively, these studies suggest that the soluble nNOSβ is responsible for the increased renal cortical NO production during pregnancy.

scholarly journals Blood lipid profile of female and male rats in case of toxic cardiomyopathy, due to the introduction of sodium nitrite

2017 ◽  
Author(s):  
I. Ya. Krynytska ◽  
M. I. Marushchak ◽  
I. O. Stahurska ◽  
I. R. Bekus ◽  
M. V. Kyryliv ◽  
...  
Keyword(s):  
Blood Plasma ◽  
Lipid Profile ◽  
Sodium Nitrite ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Blood Lipid ◽  
Male Rats ◽  
Cholesterol Concentration ◽  
High Density Lipoproteins ◽  
Blood Lipid Profile

The indices of the blood plasma lipid profile of female and male rats in case of toxic cardiomyopathy, due to the introduction of sodium nitrite were sudied. It was determined the increasing of cholesterol concentration in the blood plasma and its redistribution between lipoproteins due to reduction in high density lipoproteins and an increase in low-density lipoprotein, which have proatherogenic properties in animals of both sexes. In gender comparison of changes in blood lipid profile in case of sodium nitrite intoxication their significant prevalence in male rats was found. 

scholarly journals Ultrasonographic Signs of Poor Pregnancy Outcome

2017 ◽  
Vol 11 (1) ◽  
pp. 44-58
Author(s):  
Lucía Serrano-González ◽  
María Martinez-Moya ◽  
María Platero-Mihi ◽  
José Bajo-Arenas ◽  
Tirso Perez-Medina
Keyword(s):  
Pregnancy Outcome ◽  
Imaging Techniques ◽  
Three Dimensional ◽  
Normal Pregnancy ◽  
Abdominal Wall Defects ◽  
Crown Rump Length ◽  
Additional Information ◽  
Caudal Regression ◽  
3D Volume ◽  
Poor Pregnancy Outcome

ABSTRACT The frequency of spontaneous abortion, when it is considered from its very beginning, along with the theoretical knowledge of the causes of the abortion, should provide a perspective to the obstetrician that, performing a sonographic exploration finds discoveries that cannot correspond to those characterizing a normal pregnancy. The precocity of the realization of sonographic explorations in the pregnancy will allow diagnosis of many more cases of spontaneous interruptions of the development of pregnancy. New sonographic imaging techniques including three-dimensional (3D) sonography can provide additional information regarding the presence of structural anomalies via 3D volume acquisition, like craniofacial deformities, clefts, neural tube defects, abdominal wall defects, and caudal regression syndrome. It may give further details regarding the timing of embryonic/fetal demise in early pregnancy. Sufficient informational value is regularly obtained in cases having a crown-rump length >8 mm. How to cite this article Serrano-González L, Martinez-Moya M, Platero-Mihi M, Bajo-Arenas J, Perez-Medina T. Ultrasonographic Signs of Poor Pregnancy Outcome. Donald School J Ultrasound Obstet Gynecol 2017;11(1):44-58.

Sign in / Sign up

Export Citation Format

Share Document