scholarly journals The impact of reduced uterine perfusion pressure on ascorbic acid status in pregnant rats

2006 ◽  
Vol 20 (5) ◽  
Author(s):  
Rolando Juan Jose Ramirez ◽  
Jacqueline Novak
Keyword(s):  
Ascorbic Acid ◽  
Perfusion Pressure ◽  
Pregnant Rats ◽  
Acid Status ◽  
Uterine Perfusion ◽  
The Impact

scholarly journals Induction of heme oxygenase-1 shifts the balance from proinjury to prosurvival in the placentas of pregnant rats with reduced uterine perfusion pressure

2012 ◽  
Vol 302 (5) ◽  
pp. R620-R626 ◽  
Author(s):  
Eric M. George ◽  
Istvan Arany
Keyword(s):  
Oxidative Stress ◽  
Heme Oxygenase ◽  
Caspase 3 ◽  
Perfusion Pressure ◽  
Atp Depletion ◽  
Heme Oxygenase 1 ◽  
Pregnant Rats ◽  
Intracellular Atp ◽  
Uterine Perfusion ◽  
The Impact

Placental hypoxia/ischemia has been implicated as a central factor in the development of preeclampsia. One particularly useful animal model to study the impact of placental ischemia is the reduced uterine perfusion pressure (RUPP) model. We have previously demonstrated that RUPP animals exhibit elevated placental oxidative stress, which plays an important role in the development of the associated maternal hypertension. Recently, we have demonstrated that cobalt protoporphyrin (CoPP)-mediated induction of heme oxygenase-1 (HO-1) attenuates RUPP-induced oxidative stress and consequent hypertension. However, signaling pathways that are involved in this process are virtually unknown. Here, we show that placentas from RUPP animals exhibit increased phosphorylation of JNK, STAT1, STAT3, and p52shc with a concomitant increase in caspase-3 activation and depletion of intracellular ATP. Treatment with CoPP decreased RUPP-induced phosphorylation of JNK and STAT1, while it increased phosphorylation of ERK and STAT3, leading to decreased caspase-3 activation and restoration of intracellular ATP content. Our data imply that RUPP induces oxidative stress and the consequent injurious state by increasing phosphorylation of mediators of injury (STAT1, JNK) and, to a lesser extent, survival (STAT3, p52shc) in placentas of pregnant rats. HO-1 induction shifts this balance to a prosurvival phenotype by augmenting phosphorylation of the prosurvival ERK and STAT3, while suppressing phosphorylation of JNK and STAT1. This attenuates the resulting injury, as indicated by caspase-3 activation and ATP depletion. These results demonstrate a novel therapeutic activity of HO-1 induction in placental cell survival during ischemia and support the HO-1 pathway as a promising therapeutic target for the management of preeclampsia.

scholarly journals Characterisation of cardiac health in the reduced uterine perfusion pressure model and a 3D cardiac spheroid model, of preeclampsia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Claire Richards ◽  
Kimberly Sesperez ◽  
Michael Chhor ◽  
Sahar Ghorbanpour ◽  
Claire Rennie ◽  
...  
Keyword(s):  
Perfusion Pressure ◽  
Late Onset ◽  
Cardiac Fibroblasts ◽  
Immunofluorescent Staining ◽  
Collagen Deposition ◽  
Human Coronary Artery ◽  
Pregnant Rats ◽  
Cardiac Health ◽  
Increased Risk ◽  
Uterine Perfusion

Abstract Background Preeclampsia is a dangerous cardiovascular disorder of pregnancy that leads to an increased risk of future cardiovascular and metabolic disorders. Much of the pathogenesis and mechanisms involved in cardiac health in preeclampsia are unknown. A novel anti-angiogenic protein, FKBPL, is emerging as having a potential role in both preeclampsia and cardiovascular disease (CVD). Therefore, in this study we aimed to characterise cardiac health and FKBPL regulation in the rat reduced uterine perfusion pressure (RUPP) and a 3D cardiac spheroid model of preeclampsia. Methods The RUPP model was induced in pregnant rats and histological analysis performed on the heart, kidney, liver and placenta (n ≥ 6). Picrosirius red staining was performed to quantify collagen I and III deposition in rat hearts, placentae and livers as an indicator of fibrosis. RT-qPCR was used to determine changes in Fkbpl, Icam1, Vcam1, Flt1 and Vegfa mRNA in hearts and/or placentae and ELISA to evaluate cardiac brain natriuretic peptide (BNP45) and FKBPL secretion. Immunofluorescent staining was also conducted to analyse the expression of cardiac FKBPL. Cardiac spheroids were generated using human cardiac fibroblasts and human coronary artery endothelial cells and treated with patient plasma from normotensive controls, early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE); n = 3. FKBPL and CD31 expression was quantified by immunofluorescent labelling. Results The RUPP procedure induced significant increases in blood pressure (p < 0.001), collagen deposition (p < 0.001) and cardiac BNP45 (p < 0.05). It also induced a significant increase in cardiac FKBPL mRNA (p < 0.05) and protein  expression  (p < 0.01). RUPP placentae also exhibited increased collagen deposition and decreased Flt1 mRNA expression (p < 0.05). RUPP kidneys revealed an increase in average glomerular size (p < 0.05). Cardiac spheroids showed a significant increase in FKBPL expression when treated with LOPE plasma (p < 0.05) and a trend towards increased FKBPL expression following treatment with EOPE plasma (p = 0.06). Conclusions The rat RUPP model induced cardiac, renal and placental features reflective of preeclampsia. FKBPL was increased in the hearts of RUPP rats and cardiac spheroids treated with plasma from women with preeclampsia, perhaps reflective of restricted angiogenesis and inflammation in this disorder. Elucidation of these novel FKBPL mechanisms in cardiac health in preeclampsia could be key in preventing future CVD.

Abstract 052: Placental Growth Factor (PlGF) Reduces Blood Pressure and Improves Endothelin Type B Receptor (ETBR)-Mediated Microvascular Dilation in Hypertensive Pregnant Rats

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Marc Q Mazzuca ◽  
Zongli Ren ◽  
Chen Lin ◽  
Jose S Possomato-Vieira ◽  
Minglin Zhu ◽  
...  
Keyword(s):  
Perfusion Pressure ◽  
Mesenteric Arteries ◽  
Hypertensive Disorder ◽  
Type B ◽  
Pregnant Rats ◽  
Western Blots ◽  
New Approach ◽  
Nitrite Production ◽  
Uterine Perfusion ◽  
Mesenteric Microvessels

Preeclampsia is a pregnancy-related hypertensive disorder (HTN-Preg) with an imbalance between anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) and angiogenic PlGF, but the vascular targets involved are unclear. We have shown downregulation of endothelial ET B R in Preg rats with reduced uterine perfusion pressure (RUPP), and studies have shown increased plasma sFlt-1 in RUPP rats. We tested if raising PIGF/sFlt-1 ratio by infusing PIGF (10 μg/kg/day) in RUPP rats would improve BP and microvascular ET B R signaling, and vice versa, if lowering PIGF/sFlt-1 ratio by infusing sFlt-1 (10 μg/kg/day) in Preg rats increases BP and reduces ET B R signaling. On day 19, BP was recorded and mesenteric microvessels were isolated for measurement of diameter and [Ca 2+ ] i (fura-2 340/380 ratio). BP was in PlGF-RUPP 105±2 < RUPP 126±1 and in sFlt-Preg 125±4 > Norm-Preg 97±5 mmHg. ET-1 vasoconstriction was in PlGF-RUPP 62.6±3.0 < RUPP 83.4±5.3 and in sFlt-Preg 76.1±4.7 > Norm-Preg 52.1±3.2%. ET-1 caused parallel increases in microvascular [Ca 2+ ] i that was in PlGF-RUPP 0.87±0.02 < RUPP 0.92±0.01 and in sFlt-Preg 0.93±0.02 > Norm-Preg 0.85±0.01. Endothelium removal or microvessel treatment with ET B R antagonist BQ-788 enhanced ET-1 vasoconstriction and [Ca 2+ ] i in Norm-Preg and PlGF-RUPP, but not RUPP or sFlt-Preg. The ET B R agonists sarafotoxin 6c (S6c) and IRL-1620 caused relaxation that was in PlGF-RUPP 42.9±10.8, 38.0±11.2% > RUPP 4.7±3.4, 7.5±2.3% and in sFlt-Preg 3.1±1.0, 5.4±1.6% < Norm-Preg 29.9±7.8, 28.0±9.1%. L-NAME partially reduced ACh- and ET B R-induced relaxation in Norm-Preg, PlGF-RUPP, but not RUPP or sFlt-Preg, suggesting that PlGF improves the decreased NO-dependent and ET B R-mediated vasorelaxation in HTN-Preg. Basal, ACh-, S6c-, and IRL-1620-induced nitrate/nitrite production was enhanced in mesenteric arteries of PIGF-RUPP and Norm-Preg vs. RUPP rats. Western blots and immunohistochemistry revealed greater levels of endothelial ET B R in PlGF-RUPP and Norm-Preg vs. RUPP and sFlt-Preg. Thus improving PlGF/sFlt-1 balance reduces BP and ET-1 vasoconstriction, and enhances ET B R-mediated NO-dependent vasodilation in RUPP rats, and could be a new approach in the management of HTN-Preg.

scholarly journals Reduced Uterine Perfusion Pressure in Pregnant Rats Impairs Cerebral Vascular Myogenic Responses

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Michael J Ryan ◽  
Emily L Gilbert ◽  
Porter H Glover ◽  
Babbette D LaMarca ◽  
Joey P Granger
Keyword(s):  
Perfusion Pressure ◽  
Pregnant Rats ◽  
Myogenic Responses ◽  
Uterine Perfusion ◽  
Cerebral Vascular

scholarly journals l-Arginine Attenuates Hypertension in Pregnant Rats With Reduced Uterine Perfusion Pressure

Hypertension ◽  
2004 ◽  
Vol 43 (4) ◽  
pp. 832-836 ◽  
Author(s):  
Barbara T. Alexander ◽  
Maria T. Llinas ◽  
Walter C. Kruckeberg ◽  
Joey P. Granger
Keyword(s):  
Perfusion Pressure ◽  
Pregnant Rats ◽  
Uterine Perfusion

scholarly journals Effect of Angiotensin II Synthesis Blockade on the Hypertensive Response to Chronic Reductions in Uterine Perfusion Pressure in Pregnant Rats

Hypertension ◽  
2001 ◽  
Vol 38 (3) ◽  
pp. 742-745 ◽  
Author(s):  
Barbara T. Alexander ◽  
Kathy Cockrell ◽  
Farrah D. Cline ◽  
Maria T. Llinas ◽  
Mona Sedeek ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Perfusion Pressure ◽  
Pregnant Rats ◽  
Uterine Perfusion

scholarly journals Melanocortin-4 Receptor Deficiency Attenuates Placental Ischemia-Induced Hypertension in Pregnant Rats

Hypertension ◽  
2019 ◽  
Vol 73 (1) ◽  
pp. 162-170 ◽  
Author(s):  
Frank T. Spradley ◽  
Ana C. Palei ◽  
Christopher D. Anderson ◽  
Joey P. Granger
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Perfusion Pressure ◽  
Wild Type ◽  
Pregnant Rats ◽  
Melanocortin 4 Receptor ◽  
Induced Hypertension ◽  
Sympathetic Nervous ◽  
Uterine Perfusion ◽  
Placental Ischemia

Preeclampsia is a pregnancy-specific disorder of new-onset hypertension linked to placental ischemia. While obesity is a major risk factor for preeclampsia, not all obese pregnant women develop pregnancy-induced hypertension or preeclampsia. Previously, we reported that placental ischemia-induced hypertension is dependent upon intact signaling of the sympathetic nervous system. Moreover, in various models of obesity, blockade of MC4R (melanocortin-4 receptor) signaling protects against the development of hypertension via suppression of the sympathetic nervous system. Less is known about this pathway during obese pregnancy. Although blockade of MC4R may lead to increased body weight during pregnancy, we tested the hypothesis that placental ischemia-induced hypertension is attenuated in obese MC4R-deficient pregnant rats. On gestational day 14, MC4R wild-type or heterozygous-deficient (MC4R-def) rats were subjected to chronic placental ischemia via the reduced uterine perfusion pressure procedure or Sham surgery then examined on gestational day 19. In Sham MC4R-def versus Sham wild-type pregnant rats, there was increased body weight, fat mass, and circulating leptin levels but they had similar fetus weights. Reduced uterine perfusion pressure reduced fetus weights in both strains. Reduced uterine perfusion pressure increased blood pressure in wild-type rats but this response was significantly attenuated in MC4R-def rats, although blood pressure was elevated in Sham MC4R-def over Sham wild-type. These data indicate that while obese MC4R-def pregnant rats have higher blood pressure during pregnancy, placental ischemia-induced hypertension is attenuated in obese MC4R-def pregnant rats. Thus, obese women with abnormal MC4R signaling may be less susceptible to the development of placental ischemia-induced hypertension.

643: Selective reduced uterine perfusion pressure in pregnant rats

2013 ◽  
Vol 208 (1) ◽  
pp. S272
Author(s):  
Mauro Schenone ◽  
Giancarlo Mari ◽  
Brian Brocato ◽  
Jacques Samson ◽  
Robert Ahokas
Keyword(s):  
Perfusion Pressure ◽  
Pregnant Rats ◽  
Uterine Perfusion
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