Reduced uterine perfusion pressure does not influence the endocannabinoid system (ECBS) transcripts in the rat model

Placenta ◽  
2013 ◽  
Vol 34 (9) ◽  
pp. A27
Author(s):  
Mauro Schenone ◽  
Zorica Janjetovic ◽  
Ramona Phinehas ◽  
Brian Brocato ◽  
Giancarlo Mari ◽  
...  
Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2797
Author(s):  
Evangeline Deer ◽  
Lorena M. Amaral ◽  
Nathan Campbell ◽  
Sarah Fitzgerald ◽  
Owen Herrock ◽  
...  

IL-2 is a cytokine released from CD4+T cells with dual actions and can either potentiate the inflammatory response or quell a chronic inflammatory response depending on its circulating concentration. IL-2 is elevated in many chronic inflammatory conditions and is increased during preeclampsia (PE). PE is characterized by new-onset hypertension during pregnancy and organ dysfunction and increasing evidence indicates that proinflammatory cytokines cause hypertension and mitochondrial (mt) dysfunction during pregnancy. The reduced uterine perfusion pressure (RUPP) model of placental ischemia is a rat model of PE that we commonly use in our laboratory and we have previously shown that low doses of recombinant IL-2 can decrease blood pressure in RUPP rats. The objective of this study was to determine the effects of a low dose of recombinant IL-2 on multi-organ mt dysfunction in the RUPP rat model of PE. We tested our hypothesis by infusing recombinant IL-2 (0.05 ng/mL) into RUPP rats on GD14 and examined mean arterial pressure (MAP), renal, placental and endothelial cell mt function compared to control RUPP. MAP was elevated in RUPP rats (n = 6) compared to controls (n = 5) (122 ± 5 vs. 102 ± 3 mmHg, p < 0.05), but was reduced by administration of LD recombinant IL-2 (107 ± 1 vs. 122 ± 5 mmHg, n = 9, p < 0.05). Renal, placental and endothelial mt ROS were significantly increased in RUPP rats compared to RUPP+ IL-2 and controls. Placental and renal respiration rates were reduced in RUPP rats compared to control rats but were normalized with IL-2 administration to RUPPs. These data indicate that low-dose IL-2 normalized multi-organ mt function and hypertension in response to placental ischemia.


Hypertension ◽  
2018 ◽  
Vol 72 (3) ◽  
pp. 703-711 ◽  
Author(s):  
Venkata Ramana Vaka ◽  
Kristen M. McMaster ◽  
Mark W. Cunningham ◽  
Tarek Ibrahim ◽  
Rebekah Hazlewood ◽  
...  

Author(s):  
Jesse N Cottrell ◽  
Alexis Witcher ◽  
Kyleigh M Comley ◽  
Mark W Cunningham ◽  
Tarek Ibrahim ◽  
...  

Preeclampsia (PE) is characterized by new onset hypertension in association with elevated natural killer (NK) cells and inflammatory cytokines which are likely culprits for decreased fetal weight during PE pregnancies. As progesterone increases during normal pregnancy, it stimulates Progesterone Induced Blocking Factor (PIBF). PIBF has been shown to decrease inflammation and cytolytic NK cells, both of whichare increased during PE. We hypothesized that PIBF reduces inflammation as a mechanism to improve hypertension in the preclinical RUPP rat model of PE. PIBF (2.0 µg/mL) was administered intraperitoneally on gestational day 15 to either RUPP or normal pregnant (NP) rats. On day 18 carotid catheters were inserted. Mean arterial blood pressure (MAP) and samples were collected on day 19. MAP in NP rats (n=11) was 100±2 mmHg and 105±3 in NP+PIBF (n=8), 122±1 in RUPP rats (n=10), which improved to 110±2 mmHg in RUPP+PIBF rats (n=11), p<0.05. Pup weight was 2.4±0.1 grams (g) in NP, 2.5±0.1 g in NP+PIBF, 1.9±0.1 g in RUPP and improved to 2.1±0.1gin RUPP+PIBF rats. Circulating and placental cytolytic NK cells, IL-17 and IL-6 were significantly reduced while IL-4 and TH2 cells were significantly increased in RUPP rats after PIBF administration. Importantly, vasoactive pathways preproendothelin-1, nitric oxide and sFlt-1 were normalized in RUPP+PIBF rats compared to RUPP rats, p<0.05. Our findings suggest that PIBF normalized IL-4/TH2 cells which was associated with improved inflammation, fetal growth restriction and blood pressure in the RUPP rat model of PE.


2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Lorena Amaral ◽  
Jose Santiago‐font ◽  
Ellen Gillis ◽  
Janae Moseley ◽  
Jennifer Sasser ◽  
...  

Hypertension ◽  
2015 ◽  
Vol 65 (1) ◽  
pp. 225-231 ◽  
Author(s):  
Lorena M. Amaral ◽  
Denise C. Cornelius ◽  
Ashlyn Harmon ◽  
Janae Moseley ◽  
James N. Martin ◽  
...  

Hypertension ◽  
2020 ◽  
Vol 75 (2) ◽  
pp. 561-568 ◽  
Author(s):  
Rachel D. Williamson ◽  
Fergus P. McCarthy ◽  
Samprikta Manna ◽  
Emer Groarke ◽  
Douglas B. Kell ◽  
...  

2016 ◽  
Vol 311 (6) ◽  
pp. R1158-R1163 ◽  
Author(s):  
Jose A. Santiago-Font ◽  
Lorena M. Amaral ◽  
Jessica Faulkner ◽  
Tarek Ibrahim ◽  
Venkata Ramana Vaka ◽  
...  

Preeclampsia is a hypertensive disorder of pregnancy that has limited therapeutic options. In healthy pregnancy, relaxin plays an important vasodilatory role to maintain vascular compliance; however, currently, there is no preclinical evidence to support the use of relaxin during preeclampsia. Therefore, the goal of this study was to test the hypothesis that recombinant human relaxin-2 (Serelaxin, Novartis; RLX) could reduce mean arterial pressure (MAP) and improve uterine artery resistance index (UARI) and nitric oxide bioavailability, and/or decrease prepro-endothelin-1 (PPET-1), soluble fms-like tyrosine kinase-1 (sFlt-1), and TNF-α) in the reduced uterine perfusion pressure (RUPP) model of preeclampsia. On day 14 of gestation (GD14), pregnant rats were assigned to normal pregnant (NP), RUPP, RUPP+RLX, or NP+RLX groups. Treated rats received RLX at 0.4 μg/h or RLX2 4 μg/h RLX via minipump implanted on GD14. On GD18, carotid arterial catheters were inserted, and on GD19, MAP and tissues were collected. MAP was increased in RUPP rats compared with NP but was lowered with either dose of RLX. UARI and sFlt-1 were significantly improved in both treated RUPP groups. Total circulating nitrate-nitrite improved and placental PPET-1 and TNF-α were significantly decreased with the higher dose of RLX. Renal cortex PPET-1 was reduced with both doses of RLX. In conclusion, Serelaxin improved blood pressure, sFlt-1, TNF-α, UARI, and nitric oxide bioavailability and PPET-1 in a rat model of preeclampsia, thereby suggesting a potential therapeutic role for RLX in maintaining maternal health and prolonging pregnancy in the face of placental ischemia.


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