bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aldosterone increases renal expression of TGFβ in a rat model of acute cyclosporine nephrotoxicity (CsA‐Nx) (690.16)
Authors: Ramírez Victoria , Cruz Cristino , Loredo Lilia , Bobadilla Norma 
Published: June 2021

Previously, we demonstrated that spironolactone (mineralocorticoid receptor antagonist) prevented renal dysfunction and reduced structural injury (SI) in rats with chronic CsA Nx, suggesting a main role of aldosterone. This nephropathy however, is only induced in the rat when renin angiotensin aldosterone system (RAAS) is activated by a low salt diet. Here, we evaluated the aldosterone contribution in SI induced by CsA in absence of RAAS activation. Forty male Wistar rats were divided into: vehicle, aldosterone infused (Aldo, 0.7mg/Kg), CsA (5mg/Kg sc) and CsA+Aldo groups. All rats were fed with a standard salt diet and followed for 14 days. Mean arterial pressure, renal blood flow, creatinine clearance, were measured, as well as lipid peroxidation as an oxidative stress marker. mRNA and protein levels of TGFβ, pSMAD3/SMAD3, endothelin and endothelin receptors (ETA and ETB) were assessed. Hypoperfusion and renal dysfunction were observed in the three experimental groups, but only in CsA+Aldo group, oxidative stress, endothelin and TGFβ signaling were significantly increased. These results suggest that structural injury induced by CsA is at least in part, mediated by aldosterone in the absence of RAAS activation by a low sodium diet.Grant Funding Source: National council of science and technology of Mexico grants numbers 155700 to VRG and 181267 to NAB
α (E)‐catenin regulates Bmp7 in tubular epithelial cells (691.3)
Authors: Nichols LaNita , Ślusarz Anna , Grunz‐Borgmann Elizabeth , Parrish Alan 
Published: June 2021

Acute kidney injury (AKI) most often occurs in a background of chronic kidney disease, both of which increase with age. Several studies have shown increased incidence and severity of AKI in aged patients. Previously, our laboratory has shown that aging is associated with a loss of α‐catenin expression in rat proximal tubular epithelium. To understand the consequences of reduced α‐catenin expression, stable α (E)‐catenin knockdown (C2) and non‐targeted control (NT3) cell lines were generated in the NRK‐52E rat proximal tubular epithelial cell line. C2 cells are marked by a significant decrease in wound repair due to alterations in cell migration. Interestingly, expression of a bone morphogenic protein, Bmp7 is significantly reduced in C2 cells. The loss of Bmp7 expression is also associated with alterations in downstream signaling. In NT3 cells, a strong nuclear staining of phospho‐Smad1/5/8 is seen, while a diffuse cytoplasmic signal is seen in C2 cells. However, shortly after addition of exogenous Bmp7, C2 cells display a similar nuclear localization as control. We then examined the role of Bmp7 in repair. Addition of exogenous Bmp7 to C2 cells rescued wound healing to levels comparable to control NT3 cells. Conversely, a Bmp7 antagonist, LDN193189, inhibits wound healing in NT3. Taken together, these results demonstrate that α‐catenin plays a role in the regulation of Bmp7.Grant Funding Source: supported by NIH RO1AAG034154
BEA‐induced acute papillary necrosis does not attenuate the enhanced RIHP response to saline volume expansion in rats (692.5)
Authors: Sánchez‐Briones M.Eugenia , López‐Rodríguez J. Francisco , Calvo Turrubiartes Miriam , LLamazares‐Azuara Lilia , Rodríguez‐Martínez Manuel 
Published: June 2021

The role of a functional renal papilla in renal interstitial hydrostatic pressure (RIHP) response to saline volume expansion (SVE, 5% bw, ~ 30 min, 0.9%) was assessed in male rats pretreated with either 0.9 % saline (CTR, 200 µl, i.a.) or 2‐bromoethylamine (BEA, 200 mg/kg, i.a.). After 7 days, RIHP (subcapsular, mmHg), renal cortical and medullary blood flows (RCBF/RMBF, L‐D, APU), urinary water (V, ml/ min/ 100 g bw), sodium (UNaV, µEq/ min/100g bw) and nitrogen oxides excretions (UNOxV, Griess, nmol/min/100g), Ht (%) and [Pr]p (g%) were measured in anesthetized animals with hormonal clamp, kidney denervation and renal perfusion pressure control at 100 mmHg (CTR: n = 9, bw = 345 ± 7 g, Uosm = 1940 ± 187 mOSM vs. BEA: n = 12, bw = 303 ± 9α g, Uosm = 371 ± 43α mOSM) during hydropenia (H), SVE, and maintained SVE (mSVE). The results are mean ± SEM. α p<0.05 between groups in the same period, * p < 0.05 vs. H in the same group.

CTR

BEA

H
SVE
mSVE
H
SVE
mSVE

Ht
51.3±0.4
45.0±*0.9
44.2±*0.8
52.6±0.7
44.0±*1.0
44.0±*1.2

[Pr]p
5.1±0.2
3.2±*0.1
2.8±*0.2
5.2±0.2
3.3±*0.2
3.2±*0.2

RIHP
4.2±0.3
27.2±*4.3
26.0±*4.8
4.1±0.6
26.0±*1.5
26.0±*2.2

UNOxV
0.46±0.1
1.8±*0.4
2.7±*0.6
0.44±0.1
1.8±*0.5
2.6±*0.7

RMBF
431±89
464±101
473±95
178±Î±54
249±Î±54
283±Î±65

UNaV
0.019±0.005
1.07±*0.16
2.53±*0.42
0.20±Î±0.06
0.86±*0.12
1.56±Î±*0.16

Conclusions: In rats, a nonfunctional renal papilla does not attenuate enhanced RIHP, UNOxV and diuretic responses to SVE, though decreases ~35% the late natriuretic response to SVE. Apparently, RMBF is a necessary but not sufficient factor for RIHP response to SVE.Grant Funding Source: Supported by IPL's financial resources
Oxidative stress and vascular reactivity changes in thoracic and abdominal aorta expose at the hyperbaric oxygenation (693.1)
Authors: Acevedo‐Villavicencio Nallely , Kormanovsky Alexander , Villanueva‐Lopez Cleva , Ramirez‐Sanchez Israel , Lara‐Padilla Eleazar , Guevara‐Balcazar Gustavo , Castillo‐Hernandez Maria 
Published: June 2021

During the hyperbaric oxygenation therapy (HBO) has been described some changes like hypoglycemia, low blood pressure, etc. The mean idea of this work is to analyze if the HBO induce some changes in the vascular reactivity and oxidative stress in healthy rats. Methods: Male rats were used (3 months old) and divided in 2 groups: with and without HBO.Rats were exposed to pure oxygen at 2 absolute atmospheres during 60 min for 3, 5, 10 and 20 sessions, after that, we obtain thoracic and abdominal aorta and were used some of the aortic rings for the isolated organ system where we made concentration response curves; and other aortic rings were used to analyze the oxidative stress. Results: changes were observed in the contractile effect to phenyleprine in both segments after HBO, without any changes in the relaxant response. On the other hand thoracic oxidative response were higher after 3 sessions of HBO, but in an interesting way we can observe that antioxidant enzyme decreased after this time; those results suggest that the antioxidant system increase the response trying to metabolize O2.Grant Funding Source: COFAA / IPN
Bestrophin‐3 expression in mouse glomeruli (694.1)
Authors: Golubinskaya Veronika , Elvin Johannes , Ebefors Kerstin , Gustafsson Helena , Mallard Carina , Nyström Jenny , Nilsson Holger 
Published: June 2021

The bestrophin isoform, bestrophin‐3 (Best3), acts as a calcium‐activated chloride channel in cardiomyocytes and in vascular smooth muscle. It may have cell‐protective functions in other cell types. Best3 may be regulated by cyclic GMP and exists in different splice variants.We have examined expression and localization of Best3 in mouse kidney on the mRNA level using RT‐PCR and on the protein level by immunohistochemistry and Western blotting.Staining for Best3 was obtained in mouse glomeruli, and was also detected in cultured mouse podocytes. Western blot confirmed the presence of Best3 protein in kidney cortex. Best3 did not co‐localize with markers for endothelial cells or podocyte foot processes. However, it co‐localized with the intermediate filament nestin, suggesting localization of Best3 in podocyte primary processes and cell bodies. In kidney cortex, in glomerulus‐enriched fractions and in cultured podocytes the two shortest splice variants, but no full‐length mRNA, were detected.In conclusion, two variants of Best3, lacking some of the predicted transmembrane segments, are expressed in podocytes in mouse kidney, and are likely co‐localized with the intermediate filaments.
Effects of allopregnanolone, a positive allosteric modulation of GABAA receptors upon stress and hypertension in Schlager genetic hypertensive mice (697.3)
Authors: Head Geoffrey , Stevenson Emily , Jackson Kristy , Abegaz Beza , Moretti John‐Luis , Gueguen Cindy , Davern Pamela 
Published: June 2021

Background: Hypertensive Schlager mice (BPH/2J) have neurogenic hypertension associated with differences in GABAA receptors compared to their normotensive counterparts (BPN/3J). Allopregnanolone is an endogenous neurosteroid reduced by chronic stress and when administered, decreases anxiety by positive allosteric modulation of GABAA receptors.Aim: To determine if allopregnanolone reduces the pressor effects of stress and basal MAP in BPH/2J mice.Methods: Male BPN/3J (n=7) and BPH/2J (n=5) mice received vehicle or allopregnanolone (5µg/hour) via subcutaneous minipumps for 2 weeks. Implanted telemetric probes enabled recording of mean arterial pressure (MAP), heart rate (HR) and activity as well as the response to aversive and non‐aversive stress tests and ganglionic blockade with pentolinium before and 7 and 14 days of treatment. Mice were perfused following stress and brains were removed for immunohistochemistry.Results: Allopregnanolone reduced systolic arterial pressure (‐8.8mmHg, P=0.01) and attenuated the depressor response to pentolinium in BPH/2J mice but had no effect upon in BPN/3J. Allopregnanolone produced marked reductions in the pressor response to both cage switch and feeding stress (‐20%, P<0.01) in BPH/2J whilst increasing the pressor response to aversive stress in BPN/3J (P<0.001). Stress induced Fos counts within the medial amygdala and paraventricular nucleus were higher in untreated BPH/2J compared to BPN/3J. Allopregnanolone reduced Fos expression and treatment abolished the difference between strains.Conclusions: The selective antihypertensive and stress inhibitory effects of allopregnanolone in BPH/2J hypertensive mice suggests that allosteric modulation of GABAA receptors at the level of the hypothalamus and amygdala may be a major cause of hypertension in this model and may offer a possible new area for the development of therapy.
Genetic control of heart weight in mouse and man (697.4)
Authors: Zhao Wenyuan , Lu Lu , Williams Robert , Chen Yuanjian , Meng Weixin , Sun Yao 
Published: June 2021

Heart weight (HW) serves not only measure of cardiac structure and function, and also as an intermediate phenotype for cardiovascular disease outcome. In humans HW is a heritable trait and has been linked to several genetic loci. Genome‐wide association study (GWAS) have identified single‐nucleotide polymorphisms in and near genes that may contribute to variability in HW. The BXD family of recombinant inbred strains comprise a large panel of isogenic but diverse strain derived by crossing C57BL/6J and DBA/2J. This genetic reference panel is a remarkable resource because genotype data (high density SNP markers) is available in GeneNetwork database; and the genomes of both parents have been sequenced. Our goal is to define genetic loci and candidate genes that control HW. There is significant variation in HW among the BXD strains_from 81 to 182 mg. A locus in chromosome 3 is responsive for a significant fraction (70%) of HW variation. The expression of candidate genes in this locus was studied using whole transcriptome analysis and qPCR for the parent strains. Morphometric measurement of the parent strains was used to evaluate the causes of HW variation. Candidate genes were compared with genes identified in GWAS. Several candidate genes in our study related with candidate genes identified in human GWAS. The best candidate genes based on this synthesis of human and mouse data include KCND3, KCNA3, SLC16A4, DDX20, and OVGP1.Grant Funding Source: NIH
Nicotinamide mononucleotide supplementation reverses vascular endothelial dysfunction and large elastic artery stiffness in old mice (698.10)
Authors: de Picciotto Natalie , Gano Lindsey , Johnson Lawrence , Eng Jason , Weber Stewart , Imai Shin‐ichiro , Mills Kathryn , Seals Douglas , Sindler Amy 
Published: June 2021

Reduced bioavailability of nicotinamide adenine dinucleotide (NAD+), a cofactor for the deacetylase sirtuin1 (SIRT1), may contribute to age‐related vascular dysfunction via oxidative stress and reduced nitric oxide (NO). We hypothesized that boosting NAD+ with the precursor nicotinamide mononucleotide (NMN) might reverse these adverse effects of aging. Old (O: 26 mo, n=14) C57 male mice had impaired ex vivo carotid artery endothelium‐dependent dilation (EDD) to acetylcholine (ACh, 60 ± 5 vs. 82 ± 3%) and NO‐mediated EDD (max dilation to ACh ‐ max dilation to ACh + L‐NAME, 37 ± 4 vs. 69 ± 5%), and increased aortic pulse wave velocity (aPWV, 467 ± 18 vs. 359 ± 8 cm/s) and elastic modulus (EM, 5899 ± 731 vs. 3307 ± 288 kPa, all p<0.05) (indices of arterial stiffness) vs. young (Y; 6 mo, n=12). In O treated with NMN (300 mg/kg/d in drinking water, 8 w) (n=10), EDD (89 ± 3%), NO‐mediated EDD (61 ± 5%), aPWV (364 ± 14 cm/s) and EM (3694 ± 315 kPa) all were improved (p<0.05 vs. O). Aorta from O had reduced expression (WB) of SIRT1 (0.7 ± 0.1 vs. 1.0 ± 0.1 AU, p=0.05 vs. Y) and increased nitrotyrosine (NT) (oxidant modification) (8.7 ± 1.1 vs. 1.0 ± 0.3 AU, p<0.05 vs. Y). In O, NMN restored SIRT1 (1.1 ± 0.1 AU) and reduced NT (4.7 ± 0.7 AU) (both p<0.05 vs. O). Increasing NAD+ bioavailability may be a novel therapy for reversing age‐related vascular dysfunction by reducing oxidative stress and restoring NO signaling.Grant Funding Source: Supported by NIH AG013038 and AG000279
Blood pressure lowering effects of the CFTR‐F508del mutation are associated with reduced arterial reactivity rather than circulating blood volume (700.1)
Authors: Peotta Veronica , Bhandary Prasad , Ogu Ugochi , Volk Kenneth , Roghair Robert 
Published: June 2021

CFTR‐F508del mutation is the most common cause of cystic fibrosis. F508del homozygous patients and female F508del carriers have decreased blood pressure (BP). We tested the hypothesis that heterozygote F508del mice have lower BP and reduced aortic contractility. By radiotelemetry, female F508del carriers had significantly lower systolic BP than wild‐type C57 controls (112±1 versus 119±2 mmHg). Although male carriers did not have lower baseline BP, they had significantly lower diastolic pressures after intraperitoneal co‐injection of isoproterenol + epinephrine (60±3 versus 78±8 mmHg). Aortas isolated from male and female F508del carriers had reduced constriction to noradrenaline (0.9±0.2 versus 2.9±0.7 mN). Inhibition of wild‐type CFTR or the inositol triphosphate receptor replicated the phenotype of F508del aortas. CFTR carrier status did not alter circulating blood volume. We conclude the CFTR‐F508del mutation decreases aortic contractility and arterial pressures. As a cAMP‐activated chloride channel that facilitates calcium mobilization, we speculate wild‐type CFTR co‐activation during beta‐adrenergic receptor stimulation buffers the vasodilatory response to catecholamines, and loss of this compensatory vasoconstrictor tone may contribute to the lower BP seen in heterozygote carriers of a CFTR‐F508del mutation.Grant Funding Source: Supported by NIH R01 HL102659
Glucagon‐like peptide‐1 receptor agonist, exenatide, enhances Ca2+ buffering by SERCA in coronary smooth muscle cells from lean, healthy Ossabaw swine (700.3)
Authors: Dineen Stacey , McKenney Mikaela , Sturek Michael 
Published: June 2021

The sarco‐endoplasmic reticulum Ca2+ ATPase (SERCA) maintains optimal SR/ER Ca2+ to avoid ER stress. Exenatide may provide cardioprotection by enhancing SERCA activity, thereby preventing ER stress. Coronary smooth muscle cells were enzymatically isolated from left anterior descending artery of lean, healthy Ossabaw swine. Cytosolic Ca2+ was digitally imaged using the fluorescent Ca2+ indicator, fura‐2. The SR store was released with caffeine in Ca2+‐free physiologic salt solution (PSS). Following caffeine, cells recovered in Ca2+‐free PSS. Cells treated with exenatide demonstrated significantly enhanced Ca2+ buffering ability as shown by the undershoot of the Ca2+ below baseline upon recovery from caffeine; ΔF0/380=‐0.054±0.005 vs. ‐0.03±0.005 (p<0.005) in untreated cells. The role of SERCA was confirmed with blockage by cyclopiazonic acid, which significantly reversed the effect of exenatide. SERCA function was further elucidated by examination of the time required for buffering of Ca2+ to baseline levels. Cells treated with exenatide demonstrated more rapid Ca2+ buffering to 100% recovery to baseline levels: t100=1.7±0.06 min vs. untreated cells, t100=1.9±0.05 min (p<0.005) but not to 50% recovery. The lack of exenatide effect on t50 shows no action on Ca2+ extrusion mechanisms; instead, the predominant action of exenatide is stimulation of SERCA.Grant Funding Source: Supported by NIH HL062552, NIH/NCATS CTSI TL1 TR000162
Uterine artery smooth muscle contractions are mediated by PKC and NO signaling mechanisms in diet‐induced obese pregnant rats (700.8)
Authors: Goulopoulou Styliani , Hannan Johanna , Webb R. Clinton 
Published: June 2021

Pre‐existing obesity increases the risk of maternal and fetal complications during gestation and is associated with systemic vascular dysfunction. We hypothesized that diet‐induced obesity would impair uterine artery contractile responses in pregnant rats. Female rats were fed for 3 weeks prior to pregnancy and throughout gestation either normal chow (LN‐Preg, n=8) or normal chow plus lard and liquid sucrose (OB‐Preg, n=8). Contractile responses to phenylephrine (PE, 10‐8 – 3x10‐5 M) were measured in isolated uterine arterial segments in late pregnancy, in the presence and absence of inhibitors of ERK1/2 (PD98059, 10‐5 M), Rho kinase (ROCK, Y27632: 10‐6 M), protein kinase C (PKC, BIM: 10‐6 M) and nitric oxide synthase (NOS, L‐NAME: 10‐4 M). OB‐Preg uterine arteries had reduced sensitivity to PE compared to LN‐Preg arteries. Inhibition of PKC reduced sensitivity to PE in OB‐Preg but not in LN‐Preg uterine arteries (‐logEC50, OB‐Preg, PE: 5.75 ± 0.087 vs. PE+BIM: 5.35 ± 0.128, p<0.05; LN‐Preg, PE: 6.07 ± 0.086, PE+BIM: 5.99 ± 0.119, p>0.05), whereas inhibition of ERK1/2 or ROCK reduced sensitivity to PE in both groups. NOS inhibition increased contractile responses to PE in OB‐Preg arteries to a greater extend as compared to LN‐Preg vessels and abolished the differences between groups (‐logEC50 in the presence of L‐NAME, OB‐Preg, 6.19 ± 0.103 vs. LN‐Preg, 6.19 ± 0.079, p>0.05). Pre‐existing obesity reduces uterine artery contractile responses to α1 adrenergic stimulation in late pregnancy and this response is mediated by PKC and NO signaling mechanisms.Grant Funding Source: Supported by NIH, SWHR
Improvement of body‐fluid dysfunction by Poria cocos in nephrotic syndrome (701.3)
Authors: Lee So Min , Lee Yun Jung , Yoon Jung Joo , Han Byung Hyuk , Kang Dae Gill , Lee Ho Sub 
Published: June 2021

Improvement of body‐fluid dysfunction by Poria cocos in nephrotic syndromeSo Min Lee 1,2, Yun Jung Lee1,2, Jung Joo Yoon1,2, Byung Hyuk Han1,2, Dae Gill Kang1,2, and Ho Sub Lee1,21College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570‐749, Republic of Korea; 2 Hanbang Body‐fluid Research Center, Wonkwang University, Shinyong‐dong, Iksan, Jeonbuk, 570‐749, Republic of KoreaAbstract Nephrotic syndrome is associated with altered renal handling of water and sodium along with changes of aquaporins (AQP) and renal epithelial Na channel (ENaC).The dried sclerotia of Poria cocos Wolf (WPC) has been used for the treatment of chronic edema and nephrosis. This study was conducted to evaluate the effects of WPC on puromycin aminonucleoside (PAN)‐induced renal functional derangement and the change of renal AQP2 and ENaC expression. The nephrotic syndrome animal models were constructed by PAN 75 mg/kg injection and then were treated with losartan (30 mg/kg/day) or WPC (200 mg/kg/day) for 7 days. Consequently, WPC group was significantly improved the proteinuria and ascites. In addition, the plasma level of triglyceride, total cholesterol, and low density lipoprotein (LDL)‐cholesterol were significantly decreased in WPC. Besides, WPC group attenuated the PAN‐induced increase in protein, and mRNA levels of AQP2 and ENaC subunit α/β. WPC was significantly suppressed PAN‐induced organic osmolytes regulator such as serum‐ and glucocorticoid‐inducible protein kinase (Sgk1), and sodium‐myo‐inositol cotransporter (SMIT) mRNA expression.Taken together, WPC improve nephrotic syndrome including proteinuria and ascites, through inhibition of AQP2 and ENaC subunit. Thus, WPC is involved in the body‐fluid regulation via inhibition of water and sodium channels against renal disorder such as edema or nephrosis.
Selected laboratory parameters and seric PRR correlation as prognostic factors in patients with preeclampsia (701.6)
Authors: Lopez‐Islas Ines , Vasquez‐Vasquez Juan Ernesto , Sanchez‐Bautista Sergio Alejandro , Garcia‐Canales Anyel Angelica , Lopez‐Sanchez Pedro 
Published: June 2021

Preeclampsia (PE) shows high maternal‐fetal morbidity. Its pathophysiology is multifactorial. Prorrenin/renin receptor (PRR), a new component of the renin‐angiotensin system, has been implicated in hypertensive disorders. Our goal was to determine if seric PRR correlates with selected laboratory parameters as prognostic factors in PE. After ethics committee approval, we selected term pregnant patients with PE from the intensive care unit (n=8), and normal pregnant patients (n= 15). Pregnancy was interrupted within 24 hrs by cesarean incision. Blood samples were collected and analyzed for cholesterol, triglycerides, albumin, calcium, uric acid (UA), Mg, lactate and C‐reactive protein before and after pregnancy termination. Body mass index (BMI) was calculated at the beginning and end of pregnancy. Our results showed that PE patients had elevated serum cholesterol, triglycerides, C‐reactive protein and hypoalbuminemia before and after delivery. BMI, UA and Mg were significantly higher and all PE patients showed significant thrombocytopenia even 24 h after cesarean. Placental weight was significantly lower. Seric PRR was higher in PE patients and positively correlated with albumin, calcium and Mg. These results suggest a close correlation of PRR with several markers and might be used as prognosis factors during PEGrant Funding Source: Supported by SIP20130546