scholarly journals Chronic exogenous hyperinsulinemia in pregnancy: a rat model of pregnancy-induced hypertension.

1998 ◽  
Vol 9 (1) ◽  
pp. 9-13
Author(s):  
E Podjarny ◽  
J Bernheim ◽  
B Katz ◽  
J Green ◽  
J Mekler ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Body Weight ◽  
Urine Volume ◽  
Fractional Excretion ◽  
Analysis Of Covariance ◽  
Sodium Reabsorption ◽  
Serum Triglycerides ◽  
Pregnant Rats ◽  
Hypertension In Pregnancy ◽  
In Pregnancy

Insulin resistance and hyperinsulinemia are associated with essential hypertension. There is also evidence of hyperinsulinemia in women who developed hypertension in pregnancy (P). The present study examines whether chronic hyperinsulinemia in pregnant rats plays a role in the development of hypertension in pregnancy. A sustained-release insulin pellet was implanted subcutaneously in 15 Wistar rats (P-INS) 1 wk before and on day 7 of pregnancy; 14 control rats were sham-implanted (P-SHAM). Tail-cuff systolic BP (SBP), serum triglycerides, glucose, insulin, renal function, and urinary excretion of Na+ and of metabolites of nitric oxide were determined throughout pregnancy. Data were analyzed by ANOVA with basal body weight as covariate analysis of covariance. Results are expressed as the mean +/- SD. Body weight; water and food intake; urine volume; creatinine clearance; and level of proteinuria at the end of pregnancy were similar in both groups. The number of fetuses was 9 +/- 2.3 in P-INS versus 11 +/- 2.4 in pregnant control rats (P < 0.05). Before mating, SBP was similar, but at the end of pregnancy SBP was 110 +/- 18 mmHg in P-INS versus 85 +/- 12 mmHg in pregnant rats (P < 0.05). Serum triglycerides and Na+ were also higher in P-INS rats. The fractional excretion of Na+ was 3.1 +/- 1.0 versus 4.4 +/- 1.5, respectively (P < 0.01). The percent increase in nitric oxide metabolite excretion was 233 +/- 14 versus 370 +/- 17%, respectively (P < 0.01). Chronic hyperinsulinemia, without sugar supplementation, and hypertriglyceridemia may cause a decrease in the synthesis of nitric oxide in P-INS rats. The development of hypertension in these rats may be associated with an impaired vasodilatation, together with an increased renal sodium reabsorption.

Chronic exogenous hyperinsulinaemia-induced hypertension in pregnant rats: effect of chronic treatment with l-arginine

2001 ◽  
Vol 100 (6) ◽  
pp. 667-671 ◽  
Author(s):  
Eduardo PODJARNY ◽  
Michael BURSZTYN ◽  
Gloria RASHED ◽  
Sidney BENCHETRIT ◽  
Bernard KATZ ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Risk Factor ◽  
Chronic Treatment ◽  
Blood Pressure Response ◽  
Urinary Metabolites ◽  
Pregnant Rats ◽  
Hypertension In Pregnancy ◽  
Induced Hypertension ◽  
In Pregnancy

Recent studies have shown that maternal hyperinsulinaemia is a risk factor for the development of hypertension in pregnancy. Experimentally, pregnant rats with chronic exogenously induced hyperinsulinaemia (P-INS rats) have increased blood pressure at the end of gestation. This is associated with a blunted elevation of the excretion of the urinary metabolites of nitrate (UNOx). In the present study, we aimed to evaluate the mechanism(s) of the increase in blood pressure in this model. Four groups were studied: normal pregnant rats (P rats), P-INS rats, P-INS rats treated with l-arginine (2 g/l in the drinking water) (l-ARG rats) and hyperinsulinaemic virgin rats (V-INS rats). Systolic blood pressure (SBP), UNOx excretion (on ingestion of a controlled low-nitrate diet), urine noradrenaline (norepinephrine) and plasma endothelin levels were evaluated. Rats were killed on day 22 of pregnancy. Five P-INS rats were not killed at this time, in order to measure SBP 30 and 60 days after delivery. Fetal number and fetal body weight were evaluated. At the end of pregnancy, a 10±3% increase in SBP was found in P-INS rats, contrasting with a fall of -15±4% in P rats (P < 0.01). In the l-ARG group at the end of pregnancy, SBP values had fallen by -14±2%, to values comparable with those of P rats. The increase in UNOx excretion was 175±38% in P rats, 106±12% in l-ARG rats and 41±8% in P-INS rats (P < 0.01 compared with P and l-ARG groups). No differences were found in the urinary excretion of noradrenaline or in the plasma levels of endothelin-1 between the pregnant groups. Fetal number was similar in all groups, but fetal body weight was lower for P-INS rats compared with P and l-ARG rats. Thus the blood pressure response to l-arginine strongly suggests that a decrease in NO availability may be the main pathogenic mechanism involved in the development of hypertension in this model.

Effect of nitric oxide synthase inhibition on cardiovascular and hormonal regulation during pregnancy in the rat

2000 ◽  
Vol 78 (5) ◽  
pp. 423-427 ◽  
Author(s):  
Yunlong Zhang ◽  
Susan Kaufman
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Plasma Renin Activity ◽  
Plasma Volume ◽  
Atrial Natriuretic Factor ◽  
Plasma Renin ◽  
Renin Activity ◽  
Pregnant Rats ◽  
Oxide Synthase ◽  
In Pregnancy

Recent studies have shown that nitric oxide (NO) biosynthesis increases in pregnancy and that inhibition of nitric oxide synthase (NOS) induces some pathological processes characteristic of preeclampsia. The current project sought to study the effect of the NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 10 µg·min-1, sc for 7 days) on plasma volume, plasma atrial natriuretic factor (ANF), plasma endothelin-1 (ET), and plasma renin activity (PRA) during gestation in conscious rats. NOS inhibition caused mean arterial pressure to increase in both virgin and 21-day pregnant rats. Plasma volume fell in the pregnant rats [L-NAME, 4.5 ± 0.3 mL·100 g-1 body wt. (n = 7) vs. D-NAME, 6.8 ± 0.2 mL·100 g-1 body wt. (n = 10); P < 0.05] but not in the virgin rats [L-NAME, 4.3 ± 0.1 mL·100 g-1 body wt. (n = 6) vs. D-NAME, 4.8 ± 0.2 mL·100 g-1 body wt. (n = 8)]. There was no effect of NOS inhibition on plasma ANF levels or PRA in either the virgin or pregnant rats. However, L-NAME did decrease plasma ET levels in the pregnant rats [L-NAME, 19.6 ± 1.6 pg·mL-1 (n = 8) vs. D-NAME, 11.6 ± 2.5 pg·mL-1 (n = 9); P < 0.05]. Our results confirm that NO is involved in cardiovascular homeostasis in pregnancy; NOS inhibition selectively reduces plasma volume in pregnant rats, thus mimicking a major pathophysiological perturbation of preeclampsia. However, it does not induce the hormonal changes characteristic of preeclampsia, namely the decrease in PRA and increase in plasma ET and ANF levels. Key words: plasma volume, preeclampsia, endothelin, atrial natriuretic factor, plasma renin activity.

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.

Can the biology of VEGF and haem oxygenases help solve pre-eclampsia?

2009 ◽  
Vol 37 (6) ◽  
pp. 1237-1242 ◽  
Author(s):  
Asif Ahmed ◽  
Melissa J. Cudmore
Keyword(s):  
Nitric Oxide ◽  
Cultured Cells ◽  
Growth Factor Receptor ◽  
Placental Tissue ◽  
Endothelial Damage ◽  
Negative Regulator ◽  
Protective Effects ◽  
Pregnant Rats ◽  
Modest Improvement ◽  
In Pregnancy

Pre-eclampsia, a pregnancy-specific multi-organ syndrome characterized by widespread endothelial damage, is a new risk factor for cardiovascular disease. No therapies exist to prevent or treat this condition, even to achieve a modest improvement in pregnancy length or birth weight. Co-administration of soluble VEGFR-1 [VEGF (vascular endothelial growth factor) receptor-1; more commonly known as sFlt-1 (soluble Fms-like tyrosine kinase-1)] and sEng (soluble endoglin) to pregnant rats elicits severe pre-eclampsia-like symptoms. These two anti-angiogenic factors are increased dramatically prior to the clinical onset of pre-eclampsia and are quite possibly the ‘final common pathway’ responsible for the accompanying signs of hypertension and proteinuria as they can be reversed by VEGF administration in animal models. HO-1 (haem oxygenase-1), an anti-inflammatory enzyme, and its metabolite, CO (carbon monoxide), exert protective effects in several organs against oxidative stimuli. In a landmark publication, we showed that the HO-1 pathway inhibits sFlt-1 and sEng in cultured cells and human placental tissue explants. Both CO and NO (nitric oxide) promote vascular homoeostasis and vasodilatation, and activation of VEGFR-1 or VEGFR-2 induced eNOS (endothelial nitric oxide synthase) phosphorylation, NO release and HO-1 expression. Our studies established the HO-1/CO pathway as a negative regulator of cytokine-induced sFlt-1 and sEng release and eNOS as a positive regulator of VEGF-mediated vascular morphogenesis. These findings provide compelling evidence for a protective role of HO-1 in pregnancy and identify it as a target for the treatment of pre-eclampsia. Any agent that is known to up-regulate HO-1, such as statins, may have potential as a therapy. Any intervention achieving even a modest prolongation of pregnancy or amelioration of the condition could have a significant beneficial health impact worldwide.

Does Endothelial Nitric Oxide Synthase Gene Variation Play a Role in the Occurrence of Hypertension in Pregnancy?

2003 ◽  
Vol 22 (2) ◽  
pp. 149-155 ◽  
Author(s):  
Elvira Grandone ◽  
Donatella Colaizzo ◽  
Pasquale Martinelli ◽  
Giuseppe Pavone ◽  
Massimo Errico ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Gene Variation ◽  
Hypertension In Pregnancy ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
In Pregnancy

Suppression of endotoxin-induced fever in near-term pregnant rats is mediated by brain nitric oxide

2007 ◽  
Vol 292 (6) ◽  
pp. R2174-R2178 ◽  
Author(s):  
Denovan P. Begg ◽  
Stephen Kent ◽  
Michael J. McKinley ◽  
Michael L. Mathai
Keyword(s):  
Nitric Oxide ◽  
Core Body Temperature ◽  
Mammalian Species ◽  
Febrile Response ◽  
Pregnant Rats ◽  
Nitric Oxide Signaling ◽  
Near Term ◽  
Brain Nitric Oxide ◽  
The Brain ◽  
In Pregnancy

Over the last three decades, experiments in several mammalian species have shown that the febrile response to bacterial endotoxin is attenuated late in pregnancy. More recent evidence has established that the expression of nitric oxide synthase (NOS) enzymes is increased in the brain late in pregnancy. The current study investigated the possible role of brain nitric oxide in mediating the phenomenon of fever suppression. Core body temperature (Tb) of near-term pregnant rats ( day 19 and 20) was measured following inhibition of brain NOS and intraperitoneal injection of LPS (50 μg/kg); they were compared with both day 15 pregnant and virgin animals. Intracerebroventricular injection with an inhibitor of NOS, NG-monomethyl-l-arginine citrate (l-NMMA; 280 μg), in near-term pregnant rats restored the febrile response to LPS. As expected, near-term dams that received intracerebroventricular vehicle + IP LPS did not increase Tb, in contrast to the 1.0 ± 0.2°C rise in Tb in dams treated with ICV l-NMMA + IP LPS ( P < 0.01). In virgin females and day 15 pregnant controls receiving this treatment, the increases in Tb were 1.5 ± 0.3°C and 1.6 ± 0.4°C, respectively. Thus, blockade of brain NOS restored the febrile response to LPS in near-term dams; at 5 h postinjection, Tb was 60–70% of that observed in virgins and day 15 pregnant animals. Intracerebroventricular l-NMMA alone did not induce a significant change in Tb in any group. These results suggest that the mechanism underlying the suppression of the febrile response in near-term pregnancy is mediated by nitric oxide signaling in the brain.

Phycocyanin Decrease Trophoblast Il-17 Expression in Preeclamptic Rat Models

2017 ◽  
Vol 9 (04) ◽  
Author(s):  
Gondo H. K. ◽  
Kusworini H. ◽  
Arsana W. ◽  
Sardjono W.
Keyword(s):  
Body Weight ◽  
Immune Functions ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Rat Models ◽  
Blue Green Algae ◽  
Tissue Invasion ◽  
Lack Of Information ◽  
Anti Inflammatory ◽  
In Pregnancy

Preeclampsia/eclampsia (PEE) was the main cause of death in pregnancy. However, until now, this disease has no adequate medical prevention for lack of its basic molecular pathomechanism. In recent years, there are growing number of study has concern trophoblast apoptosis as important trigger. Thropoblast apoptosis has been shown in many report lead to trophoblast failure to invade into endometrial tissue. Invasion failure of trophoblast was characterized with high expression of IL-17 in its tissue. Spirulina arthrospira plant or also called blue-green algae has been consumed since by the Aztec tribe. Several studies have proven that this plant have the immunomodulation properties stimulate various immune functions such as production of cytokines, chemokines and other anti-inflammatory mediators. Its active bioactive Phycocyanin (PC) has been shown have an effect as anti-inflammatory and antioxidant. Previous study has been shown that this substance has beneficial effect in preeclampsia inhibition in rat models via its inflammatory reducing effect However, there are lack of information concerning its role in trophoblast IL-17. Hence, this study is conduct to reveal its role in IL-17 expression in trophoblast in preeclampsia. Methods. This research used animal models with PE/E pregnant rat. PE/E induced by IL-6 intravein at dose 5 ng/100 g/day body weight. Animals divided in 6 groups of treatment with two groups control and four groups of PC treatment in different dose. After decapitated, uterus tissue processed to view its IL-17 expression using immunofluoresnce Result. This study has proven IL-17 reducing effect of PC in preeclampsia model of pregnant rats induced by IL -6. PC has reducing IL-17 expression significantly in trophoblast tissue of pregnant rats models induced by IL-6 at dose of 40 ng/100 kg weight. Conclusion. This study confirm that PC has a protective effect on pregnant rats preeclampsia through its inhibiton of trophoblast IL-17.

Relationship Between Nitric Oxide Synthesis and Increase in Systolic Blood Pressure in Women with Hypertension in Pregnancy

1993 ◽  
Vol 12 (1) ◽  
pp. 85-92 ◽  
Author(s):  
Iain T. Cameron ◽  
Cecile L. van Papendorp ◽  
Richard M.J. Palmer ◽  
Stephen K. Smith ◽  
Salvador Moncada
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Nitric Oxide Synthesis ◽  
Hypertension In Pregnancy ◽  
In Pregnancy
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