Abstract 206: Hyperleptinemia Increases Blood Pressure and Decreases Pup Weight in Pregnant Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Ana C Palei ◽  
Eric M George ◽  
Marietta Arany ◽  
Kathy Cockrell ◽  
Joey P Granger

While the relationship of obesity to cardiovascular disease is well recognized, it also has important implications for pregnancy outcomes. Indeed, there is compelling evidence that obesity increases the risk of preeclampsia (PE). The risk of severe and mild PE and PE occurring in early and late gestation are greater in obese and overweight women. Despite the fact that obesity is the leading attributable risk for PE in developed countries, the pathophysiological mechanisms whereby obesity and metabolic factors such as leptin increases the risk for developing PE are unclear. Hyperleptinemia over the levels seen in normal pregnancy has been associated with preeclampsia. Thus the aim of this study was to investigate whether chronic hyperleptinemia causes changes in cardiovascular, metabolic and reproductive systems of pregnant rats. On gestational day (GD) 14, Sprague Dawley rats were assigned to normal pregnant (NP, n=8) group or to NP plus Leptin group (NP+Lep, n=8), in which miniosmotic pump with leptin (0.5 μg/kg/min) was placed intraperitoneally. On GD 19, mean arterial pressure (MAP) was recorded, rats were sacrificed, and blood, placentas and pups were collected. Body weight (BW) and food intake (FI) were measured on GD 16-18. Serum leptin concentration was elevated in NP+Lep compared with NP (0.82 ± 0.05 vs 17.98 ± 2.75 ng/mL, P<0.05). Circulating insulin and glucose levels were similar in NP and NP+Lep groups (both P>0.05). MAP was higher in NP+Lep compared with NP (102.40 ± 2.38 vs 121.30 ± 8.13 mmHg, P<0.05). BW was decreased in NP+Lep compared with NP at GD 19 (330.90 ± 9.08 vs 284.10 ± 8.58 g, P<0.05), probably due to the reduced FI of the NP+Ins group compared with NP during GD 16-18 (23.45 ± 0.61 vs 8.61 ± 0.83 g/day, P<0.05). Although the number of viable fetuses per rat was similar between groups (P>0.05), fetuses and placentas of the NP+Lep group were lighter than those of the NP group (2.29 ± 0.06 vs 2.11 ± 0.06 g and 0.58 ± 0.01 vs 0.50 ± 0.02 g, respectively, both P<0.05). In conclusion, leptin increases blood pressure, despite its effect of reducing body weight during pregnancy, representing a possible mechanism to induce hypertension in preeclampsia. In addition, leptin decreases pup and placental weights, which could lead to abnormal fetal outcomes.

2016 ◽  
Vol 7 (3) ◽  
pp. 409-420 ◽  
Author(s):  
T.M. Marques ◽  
E. Patterson ◽  
R. Wall ◽  
O. O’Sullivan ◽  
G.F. Fitzgerald ◽  
...  

The aim of this study was to investigate if dietary administration of γ-aminobutyric acid (GABA)-producing Lactobacillus brevis DPC 6108 and pure GABA exert protective effects against the development of diabetes in streptozotocin (STZ)-induced diabetic Sprague Dawley rats. In a first experiment, healthy rats were divided in 3 groups (n=10/group) receiving placebo, 2.6 mg/kg body weight (bw) pure GABA or L. brevis DPC 6108 (~109microorganisms). In a second experiment, rats (n=15/group) were randomised to five groups and four of these received an injection of STZ to induce type 1 diabetes. Diabetic and non-diabetic controls received placebo [4% (w/v) yeast extract in dH2O], while the other three diabetic groups received one of the following dietary supplements: 2.6 mg/kg bw GABA (low GABA), 200 mg/kg bw GABA (high GABA) or ~109 L. brevis DPC 6108. L. brevis DPC 6108 supplementation was associated with increased serum insulin levels (P<0.05), but did not alter other metabolic markers in healthy rats. Diabetes induced by STZ injection decreased body weight (P<0.05), increased intestinal length (P<0.05) and stimulated water and food intake. Insulin was decreased (P<0.05), whereas glucose was increased (P<0.001) in all diabetic groups, compared with non-diabetic controls. A decrease (P<0.01) in glucose levels was observed in diabetic rats receiving L. brevis DPC 6108, compared with diabetic-controls. Both the composition and diversity of the intestinal microbiota were affected by diabetes. Microbial diversity in diabetic rats supplemented with low GABA was not reduced (P>0.05), compared with non-diabetic controls while all other diabetic groups displayed reduced diversity (P<0.05). L. brevis DPC 6108 attenuated hyperglycaemia induced by diabetes but additional studies are needed to understand the mechanisms involved in this reduction.


2000 ◽  
Vol 279 (2) ◽  
pp. F353-F357 ◽  
Author(s):  
Ali A. Khraibi

The objective of this study was to test the hypothesis that a decrease in renal interstitial hydrostatic pressure (RIHP) accounts for the blunted pressure natriuresis during pregnancy. RIHP was measured in nonpregnant (NP; n = 9), midterm pregnant (MP; 12–14 days after conception; n = 10), and late-term pregnant (LP; 18–21 days after conception; n = 12) female Sprague-Dawley rats at two renal perfusion pressure (RPP) levels (99 and 120 mmHg). At the lower RPP level, RIHP was 5.9 ± 0.3 mmHg for NP, 3.4 ± 0.4 mmHg for MP ( P < 0.05 vs. NP), and 2.9 ± 0.1 mmHg for LP ( P < 0.05 vs. NP) rats. The increase in RPP from 99 to 120 mmHg resulted in pressure natriuretic and diuretic responses in all groups; however, the increases in fractional excretion of sodium (ΔFENa), urine flow rate (ΔV), and ΔRIHP were significantly greater ( P < 0.05) in NP compared with both MP and LP rats. ΔFENa, ΔV, and ΔRIHP were 2.06 ± 0.28%, 81.44 ± 14.10 μl/min, and 3.0 ± 0.5 mmHg for NP; 0.67 ± 0.13%, 28.03 ± 5.28 μl/min, and 0.5 ± 0.2 mmHg for MP; and 0.48 ± 0.12%, 18.14 ± 4.70 μl/min, and 0.4 ± 0.1 mmHg for LP rats. In conclusion, RIHP is significantly lower in pregnant compared with nonpregnant rats at similar RPP levels. Also, the ability of pregnant rats to increase RIHP in response to an increase in RPP is blunted. These changes in RIHP may play an important role in the blunted pressure natriuresis and contribute to the conservation of sodium and water that is critical for fetal growth and development during normal pregnancy.


1998 ◽  
Vol 274 (6) ◽  
pp. E1057-E1066 ◽  
Author(s):  
Jian Wang ◽  
Jesline T. Alexander ◽  
Ping Zheng ◽  
Hi Joon Yu ◽  
Jordan Dourmashkin ◽  
...  

Patterns of eating behavior, body weight gain, and hormone changes were examined in normal-weight albino Sprague-Dawley rats on macronutrient diets. These diets consisted of either three separate jars with pure macronutrients, fat, carbohydrate and protein, from which to choose, or a single diet with different concentrations of fat and carbohydrate. Similar patterns on the choice-diet and single-diet paradigms were observed. During the first 7–10 days on these diets but not subsequently, the rats consuming a fat-rich diet exhibit significant hyperphagia, an increase in both total and fat intake that produces higher body weight gain. Compared with a 10% fat diet, a 30% fat diet is associated with a decline in insulin and corticosterone (CORT) levels, whereas a 60% fat diet produces an increase in circulating glucose. Levels of glucose are positively correlated with fat intake, and together these measures are consistently related to body fat. These relationships are most strongly expressed in rats that consume a fat-rich diet with >30% fat. Whereas insulin levels are also positively related to body fat, CORT is inversely related in these normal-weight subjects. In animals consuming a high-fat diet, a clear separation can be seen between “obesity-prone” (OP) rats with 100% greater body fat than “obesity-resistant” (OR) rats. The OP rats, which consume 15% more total calories, have significantly higher insulin and glucose levels. In animals that consume a diet with >30% fat, it is the OP but not the OR rats that exhibit a positive relation between fat intake, glucose levels, and body fat and reveal an additional association between carbohydrate intake, insulin, and body fat. Thus these rats on macronutrient diets exhibit distinct traits that relate behavior to hormone disturbances and adiposity and distinguish subjects that are prone vs. resistant to obesity.


2008 ◽  
Vol 295 (5) ◽  
pp. H1974-H1981 ◽  
Author(s):  
Jussara M. do Carmo ◽  
John E. Hall ◽  
Alexandre A. da Silva

This study tested whether leptin restores sympathetic-vagal balance, heart rate (HR) variability, and cardiac baroreflex sensitivity (BRS) in streptozotocin (STZ)-induced diabetes. Sprague-Dawley rats were instrumented with arterial and venous catheters, and a cannula was placed in the lateral ventricle for intracerebroventricular (ICV) leptin infusion. Blood pressure (BP) and HR were monitored by telemetry. BRS and HR variability were estimated by linear regression between HR and BP responses to phenylephrine or sodium nitroprusside and autoregressive spectral analysis. Measurements were made during control period, 7 days after induction of diabetes, and 7 days after ICV leptin infusion. STZ diabetes was associated with hyperglycemia (422 ± 17 mg/dl) and bradycardia (−79 ± 4 beats/min). Leptin decreased glucose levels (165 ± 16 mg/dl) and raised HR to control values (303 ± 10 to 389 ± 10 beats/min). Intrinsic HR (IHR) and chronotropic responses to a full-blocking dose of propranolol and atropine were reduced during diabetes (260 ± 7 vs. 316 ± 6, −19 ± 2 vs. −43 ± 6, and 39 ± 3 vs. 68 ± 8 beats/min), and leptin treatment restored these variables to normal (300 ± 7, −68 ± 10, and 71 ± 8 beats/min). Leptin normalized BRS (bradycardia, −2.6 ± 0.3, −1.7 ± 0.2, and −3.0 ± 0.5; and tachycardia, −3.2 ± 0.4, −1.9 ± 0.3, and −3.4 ± 0.3 beats·min−1·mmHg−1 for control, diabetes, and leptin) and HR variability (23 ± 4 to 11 ± 1.5 ms2). Chronic glucose infusion to maintain hyperglycemia during leptin infusion did not alter the effect of leptin on IHR but abolished the improved BRS. These results show rapid impairment of autonomic nervous system control of HR after the induction of diabetes and that central nervous system actions of leptin can abolish the hyperglycemia as well as the altered IHR and BRS in STZ-induced diabetes.


1986 ◽  
Vol 2 (3) ◽  
pp. 261-271 ◽  
Author(s):  
Melissa S. Tassinari ◽  
Phyllis J. Mullenix ◽  
Paul A. Moore

Recent evidence has indicated that the anesthetic gas nitrous oxide (N20) is teratogenic to rats if exposed during the organogenesis phase of gestation. Little is known, however, of the anatomical or functional consequences of exposures occurring later in gestation when the brain is developing. Timed pregnant Sprague-Dawley rats were exposed to 75% N2O/25% O2 using one of the following pro tocols: 24 hr exposures on gestational days 11-15 or 16-20; or 8 hr exposures on gestational days 9-13, 11-15, 14-15 or day 1 5 only. Both 24 hr exposure protocols significantly reduced fetal and ma ternal body weight, an effect not observed after the 8 hr exposures. No N20 exposure resulted in gross morphological or skeletal changes. Likewise, no significant effects on total protein and DNA levels in fetal liver and brain tissues could be found subsequent to 24 hr exposures on days 16-20; or on one, three or six days follow ing an 8 hr exposure on day 15. Evaluations of postnatal growth and neurological development in pups prenatally exposed for 8 hr on days 14 and 15 revealed two noteworthy effects. Their rate of growth in body weight was greater with respect to controls between the ages of 14 and 21 days, especially in the males. Also, reflex sus pension was reduced, significantly so in the females. In conclusion, unlike 24 hr exposures, multiple 8 hr exposures to nitrous oxide during the middle to late stages of gestation did not produce effects detectable with standard teratological measures. Subtle differences in growth rate and reflex suspension, however, indicated that nor mal development had been interrupted, but its clear distinction as a lasting effect requires additional measures of function.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Nur Fathiah Abdul Sani ◽  
Levin Kesu Belani ◽  
Chong Pui Sin ◽  
Siti Nor Amilah Abdul Rahman ◽  
Srijit Das ◽  
...  

Diabetic complications occur as a result of increased reactive oxygen species (ROS) due to long term hyperglycaemia. Honey and ginger have been shown to exhibit antioxidant activity which can scavenge ROS. The main aim of this study was to evaluate the antioxidant and antidiabetic effects of gelam honey, ginger, and their combination. Sprague-Dawley rats were divided into 2 major groups which consisted of diabetic and nondiabetic rats. Diabetes was induced with streptozotocin intramuscularly (55 mg/kg body weight). Each group was further divided into 4 smaller groups according to the supplements administered: distilled water, honey (2 g/kg body weight), ginger (60 mg/kg body weight), and honey + ginger. Body weight and glucose levels were recorded weekly, while blood from the orbital sinus was obtained after 3 weeks of supplementation for the estimation of metabolic profile: glucose, triglyceride (TG), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH): oxidized glutathione (GSSG), and malondialdehyde (MDA). The combination of gelam honey and ginger did not show hypoglycaemic potential; however, the combination treatment reduced significantly (P<0.05) SOD and CAT activities as well as MDA level, while GSH level and GSH/GSSG ratio were significantly elevated (P<0.05) in STZ-induced diabetic rats compared to diabetic control rats.


2012 ◽  
Vol 303 (6) ◽  
pp. H639-H657 ◽  
Author(s):  
Joris van Drongelen ◽  
Carlijn R. Hooijmans ◽  
Frederik K. Lotgering ◽  
Paul Smits ◽  
Marc E. A. Spaanderman

The vascular response to pregnancy has been frequently studied in mesenteric artery models by investigating endothelial cell (EC)- and smooth muscle cell (SMC)-dependent responses to mechanical (flow-mediated vasodilation, myogenic reactivity, and vascular compliance) and pharmacological stimuli (G protein-coupled receptor responses: GqEC, GsSMC, GqSMC). It is unclear to what extent these pathways contribute to normal pregnancy-induced vasodilation across species, strains, and/or gestational age and at which receptor level pregnancy affects the pathways. We performed a meta-analysis on responses to mechanical and pharmacological stimuli associated with pregnancy-induced vasodilation of mesenteric arteries and included 55 (188 responses) out of 398 studies. Most included studies (84%) were performed in Wistar and Sprague-Dawley rats (SDRs) and compared late gestation versus nonpregnant controls (80%). Pregnancy promotes flow-mediated vasodilation in all investigated species. Only in SDRs, pregnancy additionally stimulates both vasodilator GqEC sensitivity (EC50 reduced by −0.76 [−0.92, −0.60] log[M]) and GsSMC sensitivity (EC50 reduced by −0.51 [−0.82, −0.20] log[M]), depresses vasopressor GqSMC sensitivity (EC50 increase in SDRs by 0.23 [0.16, 0.31] log[M]), and enhances arterial compliance. We conclude that 1) pregnancy facilitates flow-mediated vasodilation at term among all investigated species, and the contribution of additional vascular responses is species and strain specific, and 2) late pregnancy mediates vasodilation through changes at the receptor level for the substances tested. The initial steps of vasodilation in early pregnancy remain to be elucidated.


2021 ◽  
Author(s):  
Mariam Alawadhia ◽  
Farah Al Shammari ◽  
Fatemah Mulla Ali ◽  
Rama Almatar ◽  
Ayat Al-Duwaikhi ◽  
...  

Abstract BackgroundDexamethasone (DEX) induces intrauterine growth restriction (IUGR) in pregnant rats. IUGR can occur due to apoptosis of trophoblasts, which is believed to be inhibited by progesterone (P4). A group of genes called MTAs play a role in proliferation and apoptosis. MTA1 upregulates trophoblasts proliferation and differentiation, while MTA3 downregulates proliferation and induces apoptosis. Hence, we hypothesized that during IUGR, placental MTA1 decreases and MTA3 increases and this is reversed by P4 treatment. MethodsPregnant Sprague-Dawley rats were divided into 4 groups based on daily intraperitoneal injections: control (C, saline), DEX (DEX, 0.2 mg/kg/day), DEX and P4 (DEX + P4, DEX: 0.2 mg/kg/day, P4: 5 mg/kg/day) and P4-treated (P4, 5 mg/kg/day) groups. Injections were started on 15 dg until the day of dissection (19 or 21 dg). Gene and protein expressions of MTA1 and MTA3 were studied in the labyrinth (LZ) and basal (BZ) zones using real-time PCR and Western blotting, respectively. ResultsDEX treatment induced 18% reduction in fetal body weight (p<0.001) and 30% reduction in placental weight (p<0.01). Maternal P4 level was also significantly lower in DEX treated groups (p<0.05). MTA1 expression was decreased in the LZ (gene, p< 0.001) and BZ (protein p<0.01), while MTA3 protein expression was upregulated in the LZ with DEX treatment (p<0.001). These changes were reversed with P4 treatment. ConclusionThe findings of the present study indicate that DEX induces IUGR through changing the expression of placental MTA1 and MTA3 antigens and P4 improved pregnancy outcome by preventing the changes in MTAs expression.


2021 ◽  
Vol 26 (3) ◽  
pp. 307-314
Author(s):  
Young-Hyeon Lee ◽  
Min-Ho Yeo ◽  
Seon-A Yoon ◽  
Ho-Bong Hyun ◽  
Young-Min Ham ◽  
...  

1979 ◽  
Vol 236 (5) ◽  
pp. H665-H671
Author(s):  
J. M. Rojo-Ortega ◽  
F. P. Queiroz ◽  
J. Genest

Malignant hypertension was induced in Sprague-Dawley rats by a complete aortic ligation above the left renal artery. The effects of saline (0.9% NaCl) administration on the development and course of the malignant hypertensive vascular disease were studied and the treated rats were compared to non-saline-treated animals and to sham-operated controls in the early and chronic phases of the disease. In the early phase, blood pressure, hematocrit, body weight, and hypertensive vascular disease were characteristic of the malignant hypertensive process and were without significant difference in saline- and non-saline-treated animals. In contrast, the sham-operated rats remained normotensive and did not present abnormal histological findings. Plasma renin activity although decreased in the hypertensive saline-treated animals was not suppressed. In the chronic phase, NaCl administration caused an average increase of 40 g body weight during the 1-wk period this solution was given, but did not result in any improvement in blood pressure levels and vascular disease in treated rats compared to non-saline-treated animals.


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