Hindlimb unweighting alters endothelium-dependent vasodilation and ecNOS expression in soleus arterioles

The purpose of this study was to test the hypothesis that endothelium-dependent dilation is impaired in soleus resistance arteries from hindlimb-unweighted (HLU) rats. Male Sprague-Dawley rats (300–350 g) were exposed to HLU ( n = 14) or weight-bearing control (Con, n = 14) conditions for 14 days. After the 14-day treatment period, soleus first-order (1A) arterioles were isolated and cannulated with micropipettes to assess vasodilator responses to an endothelium-dependent dilator, ACh (10−9–10−4 M), and an endothelium-independent dilator, sodium nitroprusside (SNP, 10−9–10−4 M). Arterioles from HLU rats were smaller than Con arterioles (maximal passive diameter = 140 ± 4 and 121 ± 4 μm in Con and HLU, respectively) but developed similar spontaneous myogenic tone (43 ± 3 and 45 ± 3% in Con and HLU, respectively). Arteries from Con and HLU rats dilated in response to increasing doses of ACh, but dilation was impaired in arterioles from HLU rats ( P = 0.03), as was maximal dilation to ACh (85 ± 4 and 65 ± 4% possible dilation in Con and HLU, respectively). Inhibition of nitric oxide (NO) synthase (NOS) with N ω-nitro-l-arginine (300 μM) reduced ACh dilation by ∼40% in arterioles from Con rats and eliminated dilation in arterioles from HLU rats. The cyclooxygenase inhibitor indomethacin (50 μM) did not significantly alter dilation to ACh in either group. Treatment with N ω-nitro-l-arginine + indomethacin eliminated all ACh dilation in Con and HLU rats. Dilation to sodium nitroprusside was not different between groups ( P = 0.98). To determine whether HLU decreased expression of endothelial cell NOS (ecNOS), mRNA and protein levels were measured in single arterioles with RT-PCR and immunoblot analysis. The ecNOS mRNA and protein expression was significantly lower in arterioles from HLU rats than in Con arterioles (20 and 65%, respectively). Collectively, these data indicate that HLU impairs ACh dilation in soleus 1A arterioles, in part because of alterations in the NO pathway.

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Curcumin Reduces Neuroinflammation and Improves the Impairments of Anesthetics on Learning and Memory by Regulating the Expression of miR-181a-5p

NeuroImmunoModulation ◽

10.1159/000514548 ◽

2021 ◽

pp. 1-9

Author(s):

Guizhen Liu ◽

Yuchuan Sun ◽

Fei Liu

Keyword(s):

Cognitive Impairment ◽

Protective Effect ◽

Learning And Memory ◽

Cognitive Dysfunction ◽

Inflammatory Cytokines ◽

Neuroprotective Effect ◽

Morris Water Maze Test ◽

Sprague Dawley ◽

Protein Levels ◽

Sprague Dawley Rats

Objective: The purpose of this study was to explore the role of curcumin (Cur) in isoflurane (ISO)-induced learning and memory dysfunction in Sprague-Dawley rats and further elucidate the mechanism of the protective effect produced by Cur. Methods: Rat models of cognitive impairment were established by inhaling 3% ISO. The Morris water maze test was used to assess the cognitive function of rats. ELISA and qRT-PCR were used to analyze the protein levels of pro-inflammatory cytokines and expression levels of miR-181a-5p, respectively. Results: Cur significantly improved the ISO-induced cognitive dysfunction in rats and alleviated the ISO-induced neuroinflammation. miR-181a-5p was overexpressed in ISO-induced rats, while Cur treatment significantly reduced the expression of miR-181a-5p. Overexpression of miR-181a-5p promoted the cognitive impairment and the release of inflammatory cytokines and reversed the neuroprotective effect of Cur. Conclusion: Cur has a protective effect on ISO-induced cognitive dysfunction, which may be achieved by regulating the expression of miR-181a-5p.

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Dexamethasone Suppressed LPS-Induced Matrix Metalloproteinase and Its Effect on Endothelial Glycocalyx Shedding

Mediators of Inflammation ◽

10.1155/2015/912726 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 25

Author(s):

Na Cui ◽

Hao Wang ◽

Yun Long ◽

Longxiang Su ◽

Dawei Liu

Keyword(s):

Escherichia Coli ◽

Vascular Endothelium ◽

Free Water ◽

Endothelial Glycocalyx ◽

Sprague Dawley ◽

Treatment Groups ◽

Protein Levels ◽

Sprague Dawley Rats ◽

The Matrix ◽

Rat Thoracic Aorta

The aim of this study is to determine the mechanism of sepsis-induced vascular hyperpermeability and the beneficial effect of glucocorticoid in protecting vascular endothelium. Male Sprague-Dawley rats were given either a bolus intraperitoneal injection of a nonlethal dose of LPS (Escherichia coli055:B5, 10 mg/kg, Sigma) or vehicle (pyrogen-free water). Animals of treatment groups were also given either dexamethasone (4 mg/kg, 30 min prior to LPS injection) or the matrix metalloproteinases (MMPs) inhibitor doxycycline (4 mg/kg, 30 min after LPS injection). Both activities and protein levels of MMP-2p<0.001and MMP-9p<0.001were significantly upregulated in aortic homogenates from LPS-treated rats, associated with decreased ZO-1p<0.001and syndecan-1p=0.011protein contents. Both dexamethasone and doxycycline could significantly inhibit MMPs activity and reserve the expressions of ZO-1 and syndecan-1. The inhibition of MMPs by dexamethasone was significantly lower than that by doxycycline, while the rescue of syndecan-1 expression from LPS-induced endotoxemic rat thoracic aorta was significantly higher in the dexamethasone-treated compared to the doxycycline-treatedp=0.03. In conclusion, activation of MMPs plays important role in regulating ZO-1 and syndecan-1 protein levels in LPS mediated endothelial perturbation. Both dexamethasone and doxycycline inhibit activation of MMPs that may contribute to the rescue of ZO-1 and syndecan-1 expression.

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Chronic intermittent hypoxia alters NE reactivity and mechanics of skeletal muscle resistance arteries

Journal of Applied Physiology ◽

10.1152/japplphysiol.00994.2005 ◽

2006 ◽

Vol 100 (4) ◽

pp. 1117-1123 ◽

Cited By ~ 51

Author(s):

Shane A. Phillips ◽

E. B. Olson ◽

Julian H. Lombard ◽

Barbara J. Morgan

Keyword(s):

Skeletal Muscle ◽

Intermittent Hypoxia ◽

Chronic Intermittent Hypoxia ◽

Physiological Salt Solution ◽

Ang Ii ◽

Sprague Dawley ◽

Resistance Arteries ◽

Sprague Dawley Rats ◽

Resting Tone ◽

Wall Distensibility

Although arterial dilator reactivity is severely impaired during exposure of animals to chronic intermittent hypoxia (CIH), few studies have characterized vasoconstrictor responsiveness in resistance arteries of this model of sleep-disordered breathing. Sprague-Dawley rats were exposed to CIH (10% inspired O2 fraction for 1 min at 4-min intervals; 12 h/day) for 14 days. Control rats were housed under normoxic conditions. Diameters of isolated gracilis muscle resistance arteries (GA; 120–150 μm) were measured by television microscopy before and during exposure to norepinephrine (NE) and angiotensin II (ANG II) and at various intraluminal pressures between 20 and 140 mmHg in normal and Ca2+-free physiological salt solution. There was no difference in the ability of GA to constrict in response to ANG II ( P = 0.42; not significant; 10−10–10−7 M). However, resting tone, myogenic activation, and vasoconstrictor responses to NE ( P < 0.001; 10−9–10−6 M) were reduced in CIH vs. controls. Treatment of rats with the superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (tempol; 1 mM) in the drinking water restored myogenic responses and NE-induced constrictions of CIH rats, suggesting that elevated superoxide production during exposure to CIH attenuates vasoconstrictor responsiveness to NE and myogenic activation in skeletal muscle resistance arteries. CIH also leads to an increased stiffness and reduced vessel wall distensibility that were not correctable with oral tempol treatment.

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Mechanisms of flow and ACh-induced dilation in rat soleus arterioles are altered by hindlimb unweighting

Journal of Applied Physiology ◽

10.1152/japplphysiol.00642.2001 ◽

2002 ◽

Vol 92 (3) ◽

pp. 901-911 ◽

Cited By ~ 11

Author(s):

William G. Schrage ◽

Christopher R. Woodman ◽

M. Harold Laughlin

Keyword(s):

Weight Bearing ◽

Combined Treatment ◽

Sprague Dawley ◽

Hindlimb Unweighting ◽

First Order ◽

Sprague Dawley Rats ◽

Independent Mechanism ◽

Rat Soleus Muscle ◽

Luminal Flow ◽

Oxide Synthase

The purpose of this study was to test the hypothesis that endothelium-dependent dilation (flow-induced dilation and ACh-induced dilation) in rat soleus muscle arterioles is impaired by hindlimb unweighting (HLU). Male Sprague-Dawley rats (∼300 g) were exposed to HLU or weight-bearing control (Con) conditions for 14 days. Soleus first-order (1A) and second-order (2A) arterioles were isolated, cannulated, and exposed to step increases in luminal flow at constant pressure. Flow-induced dilation was not impaired by HLU in 1A or 2A arterioles. The cyclooxygenase inhibitor indomethacin (Indo; 50 μM) did not alter flow-induced dilation in 1As or 2As. Inhibition of nitric oxide synthase (NOS) with N ω-nitro-l-arginine (l-NNA; 300 μM) reduced flow-induced dilation by 65–70% in Con and HLU 1As. In contrast, l-NNA abolished flow-induced dilation in 2As from Con rats but had no effect in HLU 2As. Combined treatment with l-NNA + Indo reduced tone in 1As and 2As from Con rats, but flow-induced dilation in the presence of l-NNA + Indo was not different from responses without inhibitors in either Con or HLU 1As or 2As. HLU also did not impair ACh-induced dilation (10−9-10−4 M) in soleus 2As.l-NNA reduced ACh-induced dilation by ∼40% in Con 2As but abolished dilation in HLU 2As. Indo did not alter ACh-induced dilation in Con or HLU 2As, whereas combined treatment withl-NNA + Indo abolished ACh-induced dilation in 2As from both groups. We conclude that flow-induced dilation (1As and 2As) was preserved after 2 wk HLU, but HLU decreased the contribution of NOS in mediating flow-induced dilation and increased the contribution of a NOS- and cyclooxygenase-independent mechanism (possibly endothelium-derived hyperpolarizing factor). In soleus 2As, ACh-induced dilation was preserved after 2-wk HLU but the contribution of NOS in mediating ACh-induced dilation was increased.

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Antiproliferative and Apoptotic Effects of Shemamruthaa, a Herbal Preparation, in 7,12-Dimethylbenz(a)Anthracene-Induced Breast Cancer Rats

Journal of Evidence-Based Complementary & Alternative Medicine ◽

10.1177/2156587215580434 ◽

2015 ◽

Vol 20 (4) ◽

pp. 259-268 ◽

Cited By ~ 1

Author(s):

Ayyakkannu Purushothaman ◽

Elumalai Nandhakumar ◽

Palanivelu Shanthi ◽

Thiruvaiyaru Panchanatham Sachidanandam

Keyword(s):

Breast Cancer ◽

Mammary Carcinoma ◽

Nuclear Antigen ◽

Herbal Preparation ◽

Sprague Dawley ◽

Protein Levels ◽

Anticancer Effects ◽

Sprague Dawley Rats ◽

Apoptotic Effects ◽

Proliferating Cell

A herbal preparation, Shemamruthaa (SM), was formulated to investigate the molecular mechanism by which it exhibits anticancer effects in mammary carcinoma bearing rats. Female Sprague-Dawley rats were used for the study, and mammary carcinoma was induced by administration of 7,12-dimethylbenz( a)anthracene, intragastrically. After 3 months of induction period, the rats were treated with SM (400 mg/kg body weight) for 14 days. Our study shows that SM-treated mammary carcinoma rats showed regression in tumor volume with concomitant increase in p53, Bax, caspase-3, and caspase-9 mRNA and protein levels compared with mammary carcinoma–induced rats. Proliferating cell nuclear antigen and anti-apoptotic Bcl-2 were markedly increased in mammary carcinoma–induced rats, whereas the SM treatment significantly decreased the expression of these proteins. The expression pattern of apoptotic signaling molecules analyzed in the present study signifies the therapeutic efficacy of SM against breast cancer.

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Ultrastructural Observations of Chronic Progressive Nephrosis in the Sprague-Dawley Rat

Veterinary Pathology ◽

10.1177/030098587401100207 ◽

1974 ◽

Vol 11 (2) ◽

pp. 153-164 ◽

Cited By ~ 35

Author(s):

J. E. Gray ◽

R. N. Weaver ◽

A. Purmalis

Keyword(s):

Epithelial Cells ◽

Granular Material ◽

Basement Membranes ◽

Common Disease ◽

Sprague Dawley ◽

Paraffin Sections ◽

Protein Levels ◽

Dense Bodies ◽

Sprague Dawley Rats ◽

Bowman's Capsule

The kidneys of 43 male Sprague-Dawley rats, mostly 12-18 months old, were examined by electron microscopy. Paraffin sections stained with the allochrome procedure and thick epoxy sections stained with toluidine blue were used to select sites of nephrotic changes. Protein levels in urine were monitored periodically. The basement membranes of affected nephrons showed a two- to threefold thickening in the capillary loops and Bowman's capsule. Epithelial cells in the glomeruli underwent compensatory changes of hypertrophy, fusion of foot processes and occasionally microvillar transformation. Dense granular material as well as protein absorption droplets formed in the epithelial cells. Epithelial cells of proximal convolutions atrophied and disappeared as the basement membrane thickened to several micrometers. An increase of dense bodies, granular material, and focal cytoplasmic degradation was observed in these cells. The ongoing irreversible deterioration of scattered nephrons suggested the designation of chronic progressive nephrosis for this common disease of Sprague-Dawley rats over 1 year old.

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Tissue Deposition of the Insect Repellent DEET and the Sunscreen Oxybenzone From Repeated Topical Skin Applications in Rats

International Journal of Toxicology ◽

10.1177/1091581810380147 ◽

2010 ◽

Vol 29 (6) ◽

pp. 594-603 ◽

Cited By ~ 12

Author(s):

Daryl J. Fediuk ◽

Tao Wang ◽

Joshua E. Raizman ◽

Fiona E. Parkinson ◽

Xiaochen Gu

Keyword(s):

Day Treatment ◽

Skin Permeation ◽

Application Site ◽

Insect Repellent ◽

Sprague Dawley ◽

Combined Application ◽

Sprague Dawley Rats ◽

Rat Astrocytes ◽

Topical Applications

Insect repellent N,N-diethyl- m-toluamide (DEET) and sunscreen oxybenzone are capable of enhancing skin permeation of each other when applied simultaneously. We carried out a cellular study in rat astrocytes and neurons to assess cell toxicity of DEET and oxybenzone and a 30-day study in Sprague-Dawley rats to characterize skin permeation and tissue disposition of the compounds. Cellular toxicity occurred at 1 µg/mL for neurons and 7-day treatment for astrocytes and neurons. DEET and oxybenzone permeated across the skin to accumulate in blood, liver, and brain after repeated topical applications. DEET disappeared from the application site faster than oxybenzone. Combined application enhanced the disposition of DEET in liver. No overt sign of behavioral toxicity was observed from several behavioral testing protocols. It was concluded that despite measurable disposition of the study compounds in vivo, there was no evidence of neurotoxicological deficits from repeated topical applications of DEET, oxybenzone, or both.

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Effect of PM2.5 Exposure On Gestational Hypertension and Fetal Size in Preeclampsia-Like Rats

10.21203/rs.3.rs-872858/v1 ◽

2021 ◽

Author(s):

Jie Gao ◽

Mei Luo ◽

Shuo Zhao ◽

Hailing Wang ◽

Xuan Li ◽

...

Keyword(s):

Mrna Expression ◽

Th17 Cells ◽

Gestational Hypertension ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Mrna And Protein Expression ◽

Fetal Size ◽

Adverse Pregnancy

Abstract Studies have reported that gestational PM2.5 exposure is associated with preeclampsia (PE) and fetal growth restriction (FGR). However, whether maternal exposure to PM2.5 causes adverse pregnancy outcomes is still largely unknown. Pregnant Sprague-Dawley rats were exposed to either filtered (FA) or PM2.5 air during the whole pregnant period. A PE-like rat model was established by intraperitoneal injection of L-NAME (300 mg/kg) from GD12 to until GD20. Systolic blood pressure (SBP), weight gain, pup weight and placental weight were measured. The percentages of rat Treg/Th17 cells and Th17-related cytokines were examined by flow cytometry. Gene expression profiles were analyzed by microarray, and the expression of differentially expressed genes were validated by qRT-PCR. The results showed that maternal PM2.5 exposure had no effect on SBP but was associated with LBW and a higher labyrinth/basal zone ratio. The percentages of splenic Th17 cells from the PM2.5 group in PE-like rats were higher than those from the FA or PM2.5 groups in healthy controls. A significantly decreased Treg/Th17 cell ratio was found in the PM2.5 group in PE-like rats. The mRNA expression of Foxp3 was downregulated, while the mRNA expression of RORα and RORγτ was upregulated after PM2.5 exposure. Furthermore, we observed that both the mRNA and protein expression of TNF-a, CCL2, CCL3 and CCR1 increased in the PM2.5 groups. Our study suggested that systemic inflammation may contribute to the development of FGR associated with PM2.5 exposure throughout pregnancy.

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A Maternal Low-protein Diet during Gestation Induces Hepatic Autophagy-related Gene Expression in a Sex-specific Manner in Sprague-Dawley Rats

British Journal Of Nutrition ◽

10.1017/s0007114521003639 ◽

2021 ◽

pp. 1-29

Author(s):

Mingzhu Cai ◽

Jie Zhang ◽

Hong Chen ◽

Yuan-Xiang Pan

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Control Diet ◽

Protein Diet ◽

Low Protein Diet ◽

Related Gene ◽

Sprague Dawley ◽

Protein Levels ◽

Low Protein ◽

Sprague Dawley Rats

Abstract This study investigates the mechanism by which maternal protein restriction induces hepatic autophagy-related gene expression in the offspring of rats. Pregnant Sprague-Dawley rats were fed either a control diet (C, 18% energy from protein) or a low-protein diet (LP, 8.5% energy from protein) during gestation, followed by the control diet during lactation and post-weaning. Liver tissue was collected from the offspring at postnatal day 38 and divided into four groups according to sex and maternal diet (F-C, F-LP, M-C, and M-LP) for further analysis. Autophagy-related mRNA and protein levels were determined by real-time PCR and Western blotting, respectively. In addition, chromatin immunoprecipitation (ChIP) was performed to investigate the interactions between transcription factors and autophagy-related genes. Protein levels of p-eIF2a and ATF4 were increased only in the female offspring born to dams fed the LP diet. Correlatively, the mRNA expression of hepatic autophagy-related genes including Map1lc3b, P62/Sqstm1, Becn1, Atg3, Atg7, and Atg10 was significantly greater in the F-LP group than in the F-C group. Furthermore, ChIP results showed greater ATF4 and C/EBP homology protein (CHOP) binding at the regions of a set of autophagy-related genes in the F-LP group than in the F-C group. Our data demonstrated that a maternal LP diet transcriptionally programmed hepatic autophagy-related gene expression only in female rat offspring. This transcriptional program involved the activation of the eIF2α/ATF4 pathway and intricate regulation by transcription factors ATF4 and CHOP.

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