Abstract P091: Vitamin D Supplementation Inhibits Blood Pressure and Uterine Artery Resistance Induced by Autoantibodies to the AT1 Receptor

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Jessica L Faulkner ◽  
Mark W Cunningham ◽  
Lorena M Amaral ◽  
Tarek Ibrahim ◽  
Denise C Cornelius ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vitamin D ◽  
Uterine Artery ◽  
Resistance Index ◽  
Vitamin D Supplementation ◽  
At1 Receptor ◽  
Angiogenic Factor ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Sprague Dawley Rats

Studies in our lab have previously shown that Vitamin D supplementation in the RUPP rat model of preeclampsia lowers blood pressure and reduces autoantibodies to the AT1 receptor (AT1-AA). Therefore, we sought to determine if the effects of Vitamin D supplementation to inhibit endothelial dysfunction and hypertension during pregnancy were mediated by AT1-AA reduction. We hypothesized that Vitamin D supplementation to AT1-AA-induced hypertensive pregnant rats would reduce anti-angiogenic factor soluble FMS-like tyrosine kinase-1 (sflt-1) and uterine artery resistance index (UARI) while improving blood pressure (MAP). Purified rat AT1-AA was infused (1:40) into Sprague-Dawley rats via miniosmotic pump from gestational day (GD) 12 to GD19. On GD14-18 we administered Vitamin D2 or D3 (VD2 or VD3) to AT1-AA rats (50ul/ml) by oral gavage. On GD18 indwelling carotid catheters were inserted and UARI assessed by Doppler sonography and MAP was measured on GD19. Consistent with previous studies, MAP was 119.0 mmHg in AT1-AA infused pregnant rats. MAP was unchanged with VD2 treatment at 121.7 mmHg (n=3), however, reduced to 109.3 mmHg (n=3) in AT1-AA+VD3 rats. Pup and placental weights were 1.79 and 0.46 g (n=3), respectively, in AT1-AA rats and were increased with VD2 treatment to 2.33 and 0.54 g (n=3) and to 2.39 and 0.56 g (n=3) in AT1-AA+VD3 rats. UARI was 0.577 (n=2) in AT1-AA rats but reduced with VD2 treatment to 0.491 (n=3) and VD3 to 0.452 (n=2). Plasma sflt-1, which is increased with AT1-AA infusion, was measured with ELISA and was >1050 pg/ml in AT1-AA rats (n=3) and greatly reduced in both AT1-AA+VD2 at 42.3 pg/ml (n=2) and AT1-AA+VD3 at 241.0 pg/ml (n=3). Our preliminary data demonstrate that Vitamin D supplementation improves uterine artery vascular resistance and sflt-1 and that these are potential mechanisms for improving fetal weight and hypertension that is induced by AT1-AA during pregnancy.

scholarly journals Vitamin D supplementation reduces some AT1-AA-induced downstream targets implicated in preeclampsia including hypertension

2017 ◽  
Vol 312 (1) ◽  
pp. R125-R131 ◽  
Author(s):  
Jessica L. Faulkner ◽  
Lorena M. Amaral ◽  
Denise C. Cornelius ◽  
Mark W. Cunningham ◽  
Tarek Ibrahim ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vitamin D ◽  
Resistance Index ◽  
Vitamin D Supplementation ◽  
Type I ◽  
Ang Ii ◽  
Pregnant Rats ◽  
Factors Associated ◽  
Lower Blood ◽  
Induced Hypertension

Autoantibodies to the ANG II type I receptor (AT1-AA) are associated with preeclampsia (PE). We found that vitamin D supplementation reduced AT1-AA and blood pressure (MAP) in the RUPP rat model of PE. However, it was undetermined whether the decrease in AT1-AA was the mechanism whereby vitamin D lowered MAP or if it were through factors downstream of AT1-AA. Uterine artery resistance index, placental ET-1, and soluble FMS-like tyrosine kinase-1 are increased with AT1-AA-induced hypertension and are considered markers of PE in pregnant women. Therefore, we hypothesized that vitamin D would reduce PE factors during AT1-AA-induced hypertension and could lower blood pressure in a model of hypertension during pregnancy without PE features. Either ANG II (50 ng·kg−1·day) or AT1-AA (1:40) was infused from gestational day (GD) 12–19. vitamin D2 (VD2, 270 IU/day) or vitamin D3 (VD3, 15 IU/day) was administered orally from GD14–GD18. MAP (mmHg) increased in AT1-AA (121 ± 4) and ANG II (113 ± 1)-infused pregnant rats compared with normal pregnant rats (NP) (101 ± 2) but was lower in AT1-AA+VD2 (105 ± 2), AT1-AA+VD3 (109 ± 2), ANG II+VD2 (104 ± 4), and ANG II+VD3 (104 ± 3). VD2 and/or VD3 improved PE features associated with AT1-AA during pregnancy, while ANG II did not induce such features, supporting the hypothesis that AT1-AA induces PE features during pregnancy, and these are improved with vitamin D. In this study, we demonstrate that vitamin D improved many factors associated with PE and reduced blood pressure in a hypertensive model without PE features, indicating that vitamin D could be beneficial for various hypertensive disorders of pregnancy.

scholarly journals Early Gestational Exposure to Inhaled Ozone Impairs Maternal Uterine Artery and Cardiac Function

2020 ◽  
Author(s):  
Marcus Garcia ◽  
Raul Salazar ◽  
Thomas Wilson ◽  
Selita Lucas ◽  
Guy Herbert ◽  
...  
Keyword(s):  
Uterine Artery ◽  
Gestational Hypertension ◽  
Resistance Index ◽  
Cardiovascular Effects ◽  
Late Gestation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Transcriptional Changes ◽  
Adverse Pregnancy ◽  
Underlying Mechanisms

Abstract Exposure to air pollutants such as ozone (O3) is associated with adverse pregnancy outcomes, including higher incidence of gestational hypertension, preeclampsia, and peripartum cardiomyopathy; however, the underlying mechanisms of this association remain unclear. We hypothesized that O3 exposures during early placental formation would lead to more adverse cardiovascular effects at term for exposed dams, as compared with late-term exposures. Pregnant Sprague Dawley rats were exposed (4 h) to either filtered air (FA) or O3 (0.3 or 1.0 ppm) at either gestational day (GD)10 or GD20, with longitudinal functional assessments and molecular endpoints conducted at term. Exposure at GD10 led to placental transcriptional changes at term that were consistent with markers in human preeclampsia, including reduced mmp10 and increased cd36, fzd1, and col1a1. O3 exposure, at both early and late gestation, induced a significant increase in maternal circulating soluble FMS-like tyrosine kinase-1 (sFlt-1), a known driver of preeclampsia. Otherwise, exposure to 0.3 ppm O3 at GD10 led to several late-stage cardiovascular outcomes in dams that were not evident in GD20-exposed dams, including elevated uterine artery resistance index and reduced cardiac output and stroke volume. GD10 O3 exposure proteomic profile in maternal hearts characterized by a reduction in proteins with essential roles in metabolism and mitochondrial function, whereas phosphoproteomic changes were consistent with pathways involved in cardiomyopathic responses. Thus, the developing placenta is an indirect target of inhaled O3 and systemic maternal cardiovascular abnormalities may be induced by O3 exposure at a specific window of gestation.

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
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Normal Pregnancy ◽  
Developed Countries ◽  
Late Gestation ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Glucose Levels ◽  
Sprague Dawley Rats ◽  
Relationship Of

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.

scholarly journals Maternal vascular responses to hypoxia in a rat model of intrauterine growth restriction

2016 ◽  
Vol 311 (6) ◽  
pp. R1068-R1075 ◽  
Author(s):  
Mais M. Aljunaidy ◽  
Jude S. Morton ◽  
Christy-Lynn Cooke ◽  
Sandra T. Davidge
Keyword(s):  
Blood Pressure ◽  
Rat Model ◽  
Intrauterine Growth Restriction ◽  
Vascular Function ◽  
Uterine Artery ◽  
Resistance Index ◽  
Maternal Blood ◽  
Pregnant Rats ◽  
Intrauterine Growth ◽  
Maternal Blood Pressure

Intrauterine growth restriction (IUGR) is a common pregnancy complication and is a leading cause of fetal morbidity and mortality. Placental hypoxia contributes to adverse fetal consequences, such as IUGR. Exposing pregnant rats to hypoxia can lead to IUGR; however, assessment of maternal vascular function in a rat model of hypoxia, and the mechanisms that may contribute to adverse pregnancy outcomes, has not been extensively studied. We hypothesized that exposing pregnant rats to hypoxia will affect maternal systemic vascular function and increase the uterine artery resistance index (RI), which will be associated with IUGR. To test this hypothesis, pregnant rats were kept in normoxia (21% O2) or hypoxia (11% O2) from gestational day (GD) 6 to 20. Maternal blood pressure, uteroplacental resistance index (RI) (ultrasound biomicroscopy), and vascular function (wire myography) were assessed in uterine and mesenteric arteries. Fetal weight was significantly reduced ( P < 0.001), while maternal blood pressure was increased ( P < 0.05) in rats exposed to hypoxia. Maternal vascular function was also affected after exposure to hypoxia, including impaired endothelium-dependent vasodilation responses to methacholine in isolated uterine arteries (pEC50 normoxia: 6.55 ± 0.23 vs. hypoxia: 5.02 ± 0.35, P < 0.01) and a reduced uterine artery RI in vivo (normoxia: 0.63 ± 0.04 vs. hypoxia: 0.53 ± 0.01, P < 0.05); associated with an increase in umbilical vein RI (normoxia: 0.35 ± 0.02 vs. hypoxia: 0.45 ± 0.04, P < 0.05). These data demonstrate maternal and fetal alterations in vascular function due to prenatal exposure to hypoxia. Further, although there was a compensatory reduction in uterine artery RI in the hypoxia groups, this was not sufficient to prevent IUGR.

scholarly journals Parental vitamin D deficiency during pregnancy is associated with increased blood pressure in offspring via Panx1 hypermethylation

2016 ◽  
Vol 311 (6) ◽  
pp. H1459-H1469 ◽  
Author(s):  
Laura M. G. Meems ◽  
Hasan Mahmud ◽  
Hendrik Buikema ◽  
Jörg Tost ◽  
Sven Michel ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Nutritional Deficiencies ◽  
Sprague Dawley ◽  
Pannexin 1 ◽  
Genome Wide ◽  
Sprague Dawley Rats ◽  
Large Vessels ◽  
Increased Susceptibility

Vitamin D deficiency is one of the most common nutritional deficiencies worldwide. Maternal vitamin D deficiency is associated with increased susceptibility to hypertension in offspring, but the reasons for this remain unknown. The aim of this study was to determine if parental vitamin D deficiency leads to altered DNA methylation in offspring that may relate to hypertension. Male and female Sprague-Dawley rats were fed a standard or vitamin D-depleted diet. After 10 wk, nonsibling rats were mated. The conceived pups received standard chow. We observed an increased systolic and diastolic blood pressure in the offspring from depleted parents (F1-depl). Genome-wide methylation analyses in offspring identified hypermethylation of the promoter region of the Pannexin-1 ( Panx1) gene in F1-depl rats. Panx1 encodes a hemichannel known to be involved in endothelial-dependent relaxation, and we demonstrated that in F1-depl rats the increase in blood pressure was associated with impaired endothelial relaxation of the large vessels, suggesting an underlying biological mechanism of increased blood pressure in children from parents with vitamin deficiency. Parental vitamin D deficiency is associated with epigenetic changes and increased blood pressure levels in offspring.

scholarly journals Antibody against Na/K-ATPase Inhibitor Lowers Blood Pressure and Increases Vascular Fli1 in Experimental Preeclampsia

2019 ◽  
Vol 33 (6) ◽  
pp. 514-519 ◽  
Author(s):  
Natalia I Agalakova ◽  
Vitaly A Reznik ◽  
Olga V Nadei ◽  
Ivan A Ershov ◽  
Olga S Rassokha ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Transcription Factor ◽  
Negative Regulator ◽  
Sprague Dawley ◽  
Atpase Inhibitor ◽  
Pregnant Rats ◽  
Nuclear Transcription Factor ◽  
Protein Excretion ◽  
Sprague Dawley Rats ◽  
Umbilical Arteries

Abstract BACKGROUND Previous studies implicated cardiotonic steroids, including Na/K-ATPase inhibitor marinobufagenin (MBG), in the pathogenesis of preeclampsia (PE). We demonstrated that MBG induces fibrosis via mechanism involving inhibition of Fli1, a nuclear transcription factor and a negative regulator of collagen-1 synthesis. We hypothesized that PE blockade of increased MBG with antibody would lessen the fibrosis of umbilical arteries and lower the blood pressure in rats with PE. METHODS We tested 36 pregnant Sprague-Dawley rats in which 12 were made hypertensive by 1.8% Na supplementation (days 6–19 of gestation), 12 pregnant rats served controls. At day 19, PE rats received one intraperitoneal injection of polyclonal anti-MBG-4 antibody (0.5 ug/ml) for 4 hours. RESULTS PE was associated with higher blood pressure (117 ± 2 vs. 107 ± 2 mm Hg; P &lt; 0.01), plasma MBG levels (1.54 ± 0.34 vs. 0.49 ± 0.11 nmol/L; P &lt; 0.01), protein excretion (26 vs. 12 mg/24 hours), sFlt-1 (3-fold), decrease in Fli1 (7-fold) and increase in collagen-1 in aorta (4-fold) vs. control rats (all P &lt; 0.01). In 12 rats treated with polyclonal anti-MBG-4 antibody blood pressure dropped (93 ± 3 mm Hg) and Fli1 was decreased much less (2-fold; P &lt; 0.01 vs. nontreated rats). CONCLUSIONS These results demonstrate that in experimental PE elevated MBG level is implicated in umbilical fibrosis via suppression of Fli1.

High-dose Cholecalciferol Supplementation Reducing Morning Blood Pressure in Normotensive DM1 Patients

2020 ◽  
Vol 16 ◽  
Author(s):  
Natércia Neves Marques de Queiroz ◽  
Franciane Trindade Cunha de Melo ◽  
Fabrício de Souza Resende ◽  
Luísa Corrêa Janaú ◽  
Norberto Jorge Kzan de Souza Neto ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vitamin D ◽  
Blood Pressure Monitoring ◽  
Vitamin D Supplementation ◽  
High Dose ◽  
Before And After ◽  
Patients With Diabetes ◽  
Morning Blood Pressure ◽  
Cholecalciferol Supplementation ◽  
Lipids Profile

Background: Vitamin D (VD) deficiency has been related to several endocrine metabolic and cardiovascular diseases. Effect of VD supplementation on blood pressure (BP) in patients with diabetes is controversial. Objective: The aim of this study was to evaluate high-dose vitamin D supplementation effects on blood pressure of normotensive type 1 diabetes mellitus (T1DM) patients by 24-hour ambulatory blood pressure monitoring (ABPM). Methods: We performed a clinical trial including 35 T1DM normotensive patients, who received doses of 4,000 or 10,000 IU/day of cholecalciferol for 12 weeks according to previous VD levels. They underwent 24-hour ABPM, along with glycated hemoglobin, creatine, lipids profile and PCRus dosage before and after VD supplementation. Results and discussion: We found an expressive reduction of systolic and diastolic morning blood pressures (117±14 vs 112±14, p<0,05; 74±9 vs 70±10 mmHg, p<0,05, respectively) with no changes in other pressoric markers. Besides, we noticed a relation between levels of VD after supplementation and diastolic morning blood pressure (r= -0,4; p<0.05). Conclusion: Our study suggests an association between supplementation of high doses of vitamin D and the reduction of morning blood pressure in normotensive T1DM patients.

scholarly journals Increased superoxide levels in ganglia and sympathoexcitation are involved in sarafotoxin 6c-induced hypertension

2008 ◽  
Vol 295 (5) ◽  
pp. R1546-R1554 ◽  
Author(s):  
Melissa Li ◽  
Xiaoling Dai ◽  
Stephanie Watts ◽  
David Kreulen ◽  
Gregory Fink
Keyword(s):  
Blood Pressure ◽  
Sympathetic Innervation ◽  
Sympathetic Ganglia ◽  
Plasma Norepinephrine ◽  
Sprague Dawley ◽  
Surgical Ablation ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Induced Hypertension ◽  
Hypertension Development

Endothelin (ET) type B receptors (ETBR) are expressed in multiple tissues and perform different functions depending on their location. ETBR mediate endothelium-dependent vasodilation, clearance of circulating ET, and diuretic effects; all of these should produce a fall in arterial blood pressure. However, we recently showed that chronic activation of ETBR in rats with the selective agonist sarafotoxin 6c (S6c) causes sustained hypertension. We have proposed that one mechanism of this effect is constriction of capacitance vessels. The current study was performed to determine whether S6c hypertension is caused by increased generation of reactive oxygen species (ROS) and/or activation of the sympathetic nervous system. The model used was continuous 5-day infusion of S6c into male Sprague-Dawley rats. No changes in superoxide anion levels in arteries and veins were found in hypertensive S6c-treated rats. However, superoxide levels were increased in sympathetic ganglia from S6c-treated rats. In addition, superoxide levels in ganglia increased progressively the longer the animals received S6c. Treatment with the antioxidant tempol impaired S6c-induced hypertension and decreased superoxide levels in ganglia. Acute ganglion blockade lowered blood pressure more in S6c-treated rats than in vehicle-treated rats. Although plasma norepinephrine levels were not increased in S6c hypertension, surgical ablation of the celiac ganglion plexus, which provides most of the sympathetic innervation to the splanchnic organs, significantly attenuated hypertension development. The results suggest that S6c-induced hypertension is partially mediated by sympathoexcitation to the splanchnic organs driven by increased oxidative stress in prevertebral sympathetic ganglia.

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