bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential adaptation of glycolytic and oxidative muscles to hypoxia
Authors: De Theye Chiel Charles , Koehler S. Eleonore , Schols Annemie M.W.J. , Lamers Wouter H. , Langen Ramon J.C. 
Published: June 2021

BackgroundCOPD‐associated skeletal muscle atrophy is found in glycolytic rather than oxidative muscle fibers. We hypothesize that hypoxia is a trigger for this fiber type‐specific atrophy.MethodsMice were kept under normoxia or hypoxia. Oxygen levels were reduced stepwise to 8% during 48h, and maintained for 21 days. Food intake was monitored and mice were sacrificed at days 4 and 21.ResultsReduction of oxidative (Soleus) muscle weight was due to hypoxia‐induced hypophagia. Glycolytic (EDL) muscle weight reduction involved additional hypophagia‐independent effects. Cross sectional area (CSA) of individual fibers was reduced in glycolytic but not oxidative muscle. Expression of genes involved in proteasomal and lysosomal protein degradation, ER stress and glucocorticoid receptor (GR) signaling were increased in both muscles. In glycolytic muscle, upregulation could not be explained by hypophagia alone. Capillary contacts per fiber CSA increased in both muscles. In oxidative muscle, this was due to a reduction of the interstitial space, whereas in glycolytic muscle fiber CSA decreased.ConclusionsMuscle mass, muscle fiber CSA, proteolysis, ER‐stress and GR signaling are more affected by hypoxia in glycolytic than oxidative muscle. In oxidative, but not glycolytic muscle, these alterations are accounted for by hypophagia.Supported by the Dutch Top Institute Pharma (project # T1‐201).
GABA‐A receptors mediating sympathoinhibition elicited by moxonidine in rats
Authors: Alves Thales Biffe , Totola Leonardo T , Takakura Ana C , Colombari Eduardo , Moreira Thiago S 
Published: June 2021

The sympathoinhibition elicited by moxonidine has been attributed to activation of α2‐adrenergic/imidazoline receptors in the rostral ventrolateral medulla (RVLM) and, more recently, in the nucleus of the solitary tract (NTS). In the present study, we aimed to determine the role of the γ‐aminobutyric acid (GABA) mechanisms in the commissural NTS (cNTS) in mediating anti‐hypertensive effects of moxonidine in anesthetized normotensive rats. Mean arterial pressure (MAP) and splanchnic sympathetic nerve activity (sSNA) were recorded in urethane anaesthetized and artificially ventilated male Wistar rats (280–320 g, n = 5–7). Injections of moxonidine (2.5 and 5 nmol/50 nl) into the cNTS reduced resting MAP (105 ± 3 and 95 ± 5 mmHg, vs. pre‐injection: 117 ± 4 mmHg) and resting sSNA (92 ± 1 and 82 ± 3% of the control). The pre‐treatment with the GABA‐A antagonist bicuculline (25 pmol/50 nl) in the cNTS blocked the hypotension (Δ = −2 ± 3 mmHg, vs. moxonidine: Δ = −22 ± 4 mmHg) and sympathoinhibition (Δ = −1 ± 2%, vs. moxonidine: Δ = −18 ± 3%; p<0.05) elicited by moxonidine‐injected (5 nmol/50 nl) in the cNTS. These current data suggest that GABAergic mechanisms in the cNTS are essential for the sympathoinhibition and hypotension of moxonidine.Financial support: FAPESP; CNPq; CAPES.
Central angiotensin II induces sympathoexcitation and attenuates the open loop baroreflex gain without altering central baroreflex characteristics
Authors: Onitsuka Ken , Hosokawa Kazuya , Sakamoto Takafumi , Sakamoto Kazuo , Tobushi Tomoyuki , Fujino Takeo , Saku Keita , Matsukawa Ryuichi , Hirooka Yoshitaka , Sunagawa Kenji 
Published: June 2021

BackgroundCentral angiotensin II (ANG II) induces sympathoexcitation and hypertension. However, how ANG II impacts on the open loop baroreflex (BR) characteristics and thereby stabilization function of arterial pressure (AP) remains unknown.MethodsIn 7 anesthetized rats, we examined the acute effects of intracerebroventricular infusion of ANG II (2 ng/kg/min) on the open loop BR characteristics. We changed carotid sinus pressure (CSP) stepwise from 60 to 170 mmHg, while measuring AP and splanchnic sympathetic nerve activity (SNA). We characterized the central, peripheral and total BR loops by the CSP‐SNA relation, the SNA‐AP relation and the CSP‐AP relation, respectively.ResultsIn the central loop, ANG II markedly increased SNA (ΔSNA=57.2±17.7%, p<0.01) irrespective of CSP without attenuating the maximum gain (1.99±0.25 vs. 3.58±1.14 %/mmHg, ns) or response range (70.8±5.0 vs. 115.0±27.0%, ns). In the peripheral loop, although ANG II markedly increased AP (ΔAP=49.8±10.4 mmHg, p<0.01), the AP response plateaued in the high SNA range. In the total loop, the plateaued AP response decreased the maximum gain (1.93±0.15 vs. 0.629±0.162, p<0.01) and narrowed the response range (66.9±4.7 vs. 39.0±8.8 mmHg, p<0.01).ConclusionCentral ANG II induces sympathetically mediated hypertension and impairs AP stabilization function. This study was supported by the research grants from MEXT and MHLW, Japan.
Losartan attenuates cardiac remodeling but does not prevent vascular dysfunction in isoproterenol‐treated rats
Authors: Davel Ana Paula , Victorio Jamaira Aparecida , Clerici Stefano Piatto , Rossoni Luciana Venturini 
Published: June 2021

Overactivation of β‐adrenoceptors (β‐AR) induced by isoproterenol (Iso) results in cardiac remodeling and vascular dysfunction. We tested the hypothesis that angiotensin II (AII) via AT1 receptor could be involved in the cardiovascular effects of Iso treatment. Rats were treated with Iso (0.3 mg/kg/day, s.c.) or vehicle and co‐treated or not with the AT1 receptor antagonist losartan (Los, 40 mg/kg/day, p.o.) for one week. Mean arterial pressure and heart rate were not changed by treatments. Iso enhanced right and left ventricular mass and Los attenuated this effect. In aortas, the relaxation responses to acetylcholine and sodium nitroprusside were similar among groups. Iso increased the contractile response of aorta to phenylephrine (Phe) and Los did not alter this effect. Incubation with the inhibitor of nitric oxide (NO) synthase L‐NAME abolished differences in Phe contraction among groups. Data suggest that blockade of AT1 receptor with Los partially prevents the cardiac remodeling induced by Iso, but not the enhanced contractility of aorta related to a reduced NO modulation. Thus, AII via AT1 receptor seems do not mediate the vascular effects of β‐AR overactivity.Financial support: FAPESP/Brazil
Enhanced uterine contractility in an animal model of endometriosis
Authors: Hernandez Siomara , Cruz Myrella L , Ramirez Antonio , Torres-Reveron Annelyn , Appleyard Caroline B 
Published: June 2021

The uterus is composed of smooth muscle layers allowing its regulation. Endometriosis is defined as the presence of endometrium‐like tissue outside the uterus and is characterized by peritoneal inflammation, cysts, adhesions, infertility and chronic pelvic pain.AimInvestigate the impact of endometriosis on uterine muscle motility.MethodsEndometriosis was induced in female Sprague‐Dawley rats by suturing uterine horn tissue next to the intestinal mesentery (Endo). Sham rats had sutures only. All animals were sacrificed in estrous phase and examined for cysts. Tissues were analyzed for macroscopic and microscopic damage, myeloperoxidase (MPO) levels, and mast cell numbers. Uterine strips were mounted in organ baths to study in vitro isometric contractile responses of longitudinal and circular muscle to carbachol (10−8–10−3M).ResultsOnly Endo rats developed cysts. These animals had increased tension in uterine longitudinal muscle, more colonic damage (macroscopic 1.61 ± 0.26 vs. 1.13 ± 0.57, microscopic 4.89 ± 0.46 vs. 3.55 ± 0.45; p=0.056), more mast cells in the uterus (p<0.05), and higher MPO levels (1.5‐fold and 2‐fold for colon and uterus respectively) than Sham (n = 9 ± s.e.m.).ConclusionsOur data indicate that the pathophysiological processes associated with this animal model can influence evoked uterine contractility. R15AT006373, R25GM082406, HPD 335731 & CFRDG 335513 from NSU
Estrogen supplementation in female mice yields higher sodium (Na) retention than that of testosterone in male mice
Authors: Rouch Al , Curtis Kath , Fan Liming , Kudo Lucia , Toal Sheri , Naukam Rebecca 
Published: June 2021

Our purpose was to determine the effects of estrogen and testosterone supplementation on Na retention, blood pressure (MAP), and mRNA levels of renal Na transporters in mice. Gonadectomized female and male mice (CD1, 30–35g, 4–6 weeks old) received a pellet of 1.5 mg 17β‐estradiol (E2) and 5 mg testosterone, respectively. In metabolic cages mice consumed 1% salt diet for 10 days, 4% salt for the next 10 days, and 1% salt for the final 10 days. Na intake (Nai) and renal Na excretion (Nae) were measured daily. MAP was measured in the final 4–5 days of each period via tail‐cuff. Real‐time PCR was conducted on kidney tissue processed on the final day of each period. Nae/Nai % (mean ± se):

(n=4)
1% Salt
4% Salt
1% Salt

NF
57.3 ± 3.9
59.9 ± 2.5
54.0 ± 3.3

NM
47.9 ± 3.8
55.8 ± 2.9
48.4 ± 2.9

OE
28.3 ± 1.3*
32.4 ± 1.7*
37.8 ± 2.6*#

CT
53.5 ± 3.1
56.7 ± 3.5
47.6 ± 3.3

NF & NM: normal female and male mice, OE: ovariectomized + E2, CT: castrated + T,
‐ different from all other values (p<0.001);
‐ different from first 1% OE period (p<0.05)

MAP (mmHg) of OE mice were 95.7 ± 4.1, 79.5 ± 4.6, 93.0 ± 4.9 (1%, 4%, 1%, respectively) and not different from those of NF. PCR data showed E2‐induced upregulation of NCC, NKCC2, and ENaC mRNA.ConclusionE2 supplementation in female mice produced higher Na retention than that of T in male mice without enhancing MAP. Study supported by OCAST (OK Center for the Advancement of Science and Technology) # HR 09‐123, and OK Epscor INBRE #P20RR016478.
A new biotelemetry system to monitor blood flow velocity, blood pressure and temperature in small animals: Preliminary data from cigarette smoke exposed SH rats
Authors: Maggie Lin , Griffiths Leigh G. , Uyeminami Dale , Johnson Katherine , Pinkerton Kent E. , Pitsillides Koullis 
Published: June 2021

Telemetry monitoring of blood pressure and temperature in unrestrained rats is a relatively established procedure. However, monitoring blood pressure alone does not provide a comprehensive assessment of the physiologic changes occurring when animals are exposed to cigarette smoke. We have used a newly developed biotelemetry system capable of measuring, blood flow velocity, blood pressure and temperature in unrestrained SH rats.The biotelemetry device (EG2‐V1S2TM2, Endosomatic Systems Inc, Davis, CA) was implanted in 340–380 g SH rats under inhalational general anesthesia. A 1.5mm diameter Doppler flowprobe was attached around the abdominal aorta just caudal to the renal artery and a 1F (330μm diameter) solid state pressure sensor was inserted in the abdominal aorta at the level of the aortic trifurcation. Preliminary data from this new system show that after 30 min of 60 mg/m3 cigarette smoke exposure, average systolic flow velocity increased by 33.5% and average systolic blood pressure increased by 47% of pre‐exposure levels.The described biotelemetry system combines data from a Doppler flowprobe and a 1F high fidelity pressure sensor for making direct measurements of both blood flow velocity, blood pressure and temperature. This totally implantable telemetry system is suitable for small animals, such as rats, and provides new information regarding the effects of cigarette smoke on vascular resistance.
A Mathematical Model for a Renal Medullary Tubule Structure of Neonatal Rats
Authors: Marcano Mariano , Bonilla-Félix Melvin 
Published: June 2021

Our knowledge of the kidney in development, particularly its structure, is very limited. We used a mathematical model in conjunction with optimization problems to study the urine production capability of a medullary structure consisting of two populations of Henleˈs loops at different levels of development. In the model, the descending limb has heterogeneous transport properties along the medulla and the ascending limb only has a thick segment. The model parameters consist of membrane transport rates and boundary values for water flows and solute concentrations, and their baseline values were obtained from reported means in physiological experiments or they were estimated using physiological assumptions. By maximizing the solute free‐water absorption (FWA) and using parameter ranges from physiological experiments of neonatal rats in antidiuresis, we obtained results that yield a urine osmolality of 479 mOsmol/KgH2O and a urine flow of 0.126 nl/min per nephron. By minimizing the FWA and using parameter ranges from experiments of neonatal rats in diuresis, the results produced a urine osmolality of 75 mOsmol/KgH2O and a urine flow of 0.962 nl/min per nephron. These results are in agreement with the statement that the neonatal mammalian kidney can dilute urine as efficiently as the mature kidney, but its concentrating capability is limited.Research supported by NIH‐NIGMS grant SC1GM084744.
Tonic and reflex control of renal sympathetic nerve activity are altered by a discrete increase in sodium intake in renovascular hypertensive rats
Authors: Shimoura Caroline Gusson , Lincevicius Gisele Silvério , Bergamaschi Cassia , Campos Ruy 
Published: June 2021

Sympathoexcitation and baroreceptor dysfunction are involved in the pathophysiology of renovascular hypertension (2K1C). In the present study we investigated the effects of a discrete increase in sodium intake in 2K1C rats. Animals were divided in 4 independent groups (n=± 6/group) and treated for 2 weeks with normal sodium diet (0.5% NNa+) or high sodium diet (2% HNa+) after 4 weeks of renovascular hypertension. Water intake (WI) and urinary volume (UV) was increased in 2K1C HNa+ compared to 2K1C NNa+ (WI 2K1C HNa+ 61.1±6.4 2K1C; NNa+39.8±2.5; mL/day); UV (2K1C HNa+ 50 ± 5 mL/day; NNa+ 25.4±2.3; 2K1C). Arterial blood pressure (ABP) was significantly increased in 2K1C compared only to control group (2K1C NNa+ 174 ± 5; control NNa+ 100 ± 3 mmHg). Increased sodium intake enhanced the baroreflex sensitivity gain of HR in control and 2K1C (control NNa+ −2.6±0.7; control HNa+−5.3±0.4; 2K‐1C NNa+ −1.7±0.2; 2K‐1C HNa+ −4.1±0.6 bpm/mmHg). Renal sympathetic nerve activity (RSNA) gain was enhanced only in 2K1C HNa+(2K1C NNa+ −0.7±0.03; 2K1C HNa+ −1.4±0.06 pps/mmHg). Our results suggest that in the renovascular hypertension the improvement in the baroreceptor sensitivity to the kidney is probably a mechanism leading to increased diuresis avoiding further increase in ABP.Supported by FAPESP, CNPq
Pressure–natriuretic and hemodynamic adjustments to chronic ACE inhibition in inbred F344 and Lewis rat strains
Authors: Menzies Robert Ian , Kenyon Christopher J , Mullins John J , Bailey Matthew A 
Published: June 2021

Genetic background has a major influence on the severity of renovascular disease. Previously we showed that Lewis rats with inducible hypertension caused by transgenic renin expression have lower blood pressure, higher renal plasma flow (RPF) and glomerular filtration rate (GFR) and are relatively protected from hypertensive renal microvascular injury compared to Fisher (F344) rats. Using a congenic/consomic approach we determined that a polymorphism of the angiotensin converting enzyme (ACE) gene is a major contributory factor in explaining these strain differences.In the current study we have compared renal function in anaesthetised, non transgenic F344 and Lewis rats. Pressure‐natriuresis (PN) and pressure‐renal blood flow (PRBF) relationships were measured in groups of rats pre‐treated with and without Captopril (80mg/L drinking water 1–2wks) to inhibit ACE activity. Control F344 rats had higher baseline blood pressure and poorer PN compared with Lewis (ie shallower slope of PN curve). Captopril treatment significantly improved RBF without affecting PN in F344 rats. Conversely, Captopril reduced the slope of the PN curve in Lewis rats without affecting RBF responses to pressure. Taken together these results indicate a dominant vascular response to ACE inhibition in F344 compared with a dominant tubular response in Lewis rats.
Differential effects of ACE and chymase in the metabolism of exogenous angiotensin‐(1–12) in Wistar‐Kyoto rats
Authors: Moniwa Norihito , Varagic Jasmina , Ahmad Sarfaraz , Ferrario Carlos M. 
Published: June 2021

We examined whether angiotensin converting enzyme (ACE) or chymase is involved in the processing of angiotensin‐(1–12) [Ang‐(1–12)] in the circulation of 15 male anesthetized Wister‐Kyoto rats (WKY) at age 12–13 weeks. Rats were assigned to vehicle (Veh, saline, n=6), lisinopril (Lis, 10mg/kg, n=5) or chymostatin (10mg/kg, n=4). The saline Veh or Lis were infused intravenously 15 min prior to the administration of Ang‐(1–12) while the chymase inhibitor was administered intraperitoneally 30 min prior to Ang‐(1–12). Plasma Ang‐(1–12), Ang I, Ang II, and Ang‐(1–7) levels were measured by RIA. Peak plasma Ang‐(1–12) levels at 15 min following initiation of the infusion were not statistically different among the three treated groups while in Lis‐treated rats plasma Ang I levels rose to 3.1 versus 1.6 pmol/mL in Veh and plasma Ang II decreased to 0.3 compared with 15.2 pmol/mL in Veh. Although inhibition of chymase had no significant effect on plasma levels of Ang I and Ang II, peak concentrations of circulating Ang‐(1–7) rose to 0.75 compared with 0.43 and 0.47 pmol/mL in Veh and Lis‐treated WKY, respectively (p < 0.05). We conclude that angiotensin converting enzyme acts as the primary source for the conversion of Ang‐(1–12) in the circulation of WKY and also show for the first time a role for chymase in Ang‐(1–7) production from Ang‐(1–12).This research was supported by PO1 HL 051952.
Effects of combination therapy with valsartan and aliskiren on arterial pressure, cardiac hypertrophy and urinary protein excretion in hypertensive rats
Authors: Moniwa Norihito , Varagic Jasmina , Ahmad Sarfaraz , Ferrario Carlos M. 
Published: June 2021

We examined the effect of valsartan and aliskiren in 29 (12‐wk. old) male congenic mRen2. Lewis hypertensive rats following assignment to: vehicle (n=9), valsartan (30mg/kg/day; n=10) or valsartan combined with aliskiren (50mg/kg/day; n=10). Arterial pressure (AP) was measured by telemetry and concentrations of angiotensin‐(1–12) [Ang‐(1–12)], Ang II and Ang‐(1–7) in plasma, left ventricle (LV), kidney cortex and urine were measured by RIA 2 weeks after. Urinary angiotensinogen (U‐AGT) was measured by ELISA. Mean AP, LV weight and U‐protein excretion (UP) were reduced by valsartan and further reduced by the combined therapy. The increases in plasma Ang II induced with valsartan were reversed by the addition of aliskiren. Renal (R‐) Ang II was decreased and R‐Ang‐(1–7)/R‐Ang II ratio was increased in both treatment groups. UP correlated positively with R‐Ang II and negatively with R‐Ang‐(1–7)/R‐Ang II ratio while the reductions in U‐AGT and U‐Ang‐(1–12) in both treatment groups correlated with each other. We conclude that the more pronounced response induced by combined therapy is mediated in part through the blockade of renin and consequent decrease in Ang II levels. The changes of R‐Ang II or R‐Ang‐(1–7)/R‐Ang II ratio may explain the antiproteinuric effect of the combined therapy.This research was supported by PO1 HL 051952.
Reactivity changes in coronary artery and thoracic aorta in the gene mutant mice sgcd (B6.129 Sgcdtm1Mcn)
Authors: Marin-Romero Maria Carmen , Guevara-Balcazar Gustavo , Rosas Haydee , Coral-Vazquez Ramon Mauricio , Bobadilla-Lugo Rosa Amalia , Castillo-Hernandez Maria Carmen 
Published: June 2021

ObjectiveStudy of cardiovascular reactivity changes in the gene mutant mice sgcd.IntroductionDeletion of d‐sarcoglicano gene (delta‐SG) is related with structural and functional changes of squeletical, smooth and cardiac muscle which are related with limb‐girdle muscular dystrophy and cardiomiopathy. In this work we study the effect of some contractile and vasodilator agonist like angiotensin II and acethylcholine in this experimental model of dystrophy.MethodsWe used wild‐type and Knock‐out 5 months old female mice. We obtain thoracic aorta and the heart and both were immediately excised and placed in cold buffer, cleaned and freed from surrounding connective tissue. Isolated aortic rings and Langendorff system were maintained at 37° C, pH 7.4, were and bubbled with a mixture of 95% O2 and 5% CO2. After that we probe angiotnesin II (10−9 a 10−6M) with and without L‐NAME( sNOS antagonist) and indomethacin (COX‐1 and COX‐2 antagonist ).Results and conclusionsWe obtein significant differences between wild type and knock‐out mice, in the knock‐out mice we found an increase in the response of angiotensin II for that reason we suggest the participation of one contractile prostanoid in this effect. For that reason we decide to inhibit the contractile effect of angiotensin II with indometacin and the result was the inhibition of the contractile response. In other hand we analyse the vasodilator effect of acethylcholine at different concentrations and the result was less vasodilator effect in knock‐out mice, however we did not have differences in the vasodilator effect of nitroprusiate between wild type and knock‐out.
The Role of Eosinophils in Aspergillus fumigatus Lung Infection
Authors: Soriani Frederico , Russo Remo Castro , Nogueira Camila Rodrigues Chaves , de Sousa Lirlândia Pires , Rachid Milene , Teixeira Mauro Martins 
Published: June 2021

Eosinophils are important in the pathophysiology of allergic diseases and in host immunity. Although microorganisms directly activate inflammatory cells, the mechanisms that trigger eosinophils activation and its functions in immune responses are unknown. Fungi are ubiquitous and may contribute to the development and exacerbation of pulmonary diseases. In this sense, the aim of this study was to unravel the role of eosinophils during Aspergillus fumigatus lung infection. Wild type (BALB/c) and ΔdblGATA mice were infected intranasally with 108 spores of an A. fumigatus wild type strain. Results show that ΔdblGATA mice had increased survival (40% versus 100% in WT mice). PMN influx in the lungs (1dpi) and airways (3 dpi) were greater in ΔdblGATA mice, but there was less protein leakage (3 dpi). Levels of eosinophils were very high in lungs and airways of WT mice after A. fumigatus infection but not detectable in ΔdblGATA mice. Airway levels of CXCL1, TNF‐α, CCL11, CCL2 and IL‐1β were reduced in ΔdblGATA mice. Interestingly, histopathological analysis did not show any differences between animals. Fungal burden was higher in ΔdblGATA mice than WT mice after 1 and 3 dpi. In conclusion, the absence of eosinophils leads to decreased production of key cytokines and increased fungal burden after infection with A. fumigatus. However, this is associated with enhanced neutrophil influx and survival, suggesting that eosinophils are crucial in setting the appropriate tone of the immune response to infection by A. fumigatus.Financial Support: CNPq, Capes, FAPEMIG.