bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serine proteases affect in situ vasa recta capillary diameter: mechanism for kidney failure associated with pancreatitis?
Authors: Birch Rebecca , Crawford Carol , Kelly Mark , Unwin Robert J , Schwiebert Erik , Wildman Scott S P , Peppiatt‐Wildman Claire M 
Published: June 2021

Serine proteases are proteolytic enzymes involved in the regulation of renal function and hemodynamics. Serum trypsin (the archetypal serine protease) levels are elevated in a number of pathophysiological conditions, notably pancreatitis, which is associated with acute renal failure.Here we use the kidney slice model to investigate the effect of trypsin on vasa recta diameter in situ. Kidney slices (200 μm thick) were obtained from adult male rats as previously described [1]. Kidney slices were superfused with trypsin and DIC video imaging techniques were used to record real‐time changes in vasa recta diameter.Application of trypsin (2 U/ml) caused a significant constriction of vasa recta capillaries, specifically at smooth muscle‐like pericyte cell sites (15.5±1.4% p<0.05).Here we demonstrate that acute application of trypsin (at levels similar to those detected in patients with severe acute pancreatitis) significantly decreases vasa recta diameter and thus renal medullary blood flow, specifically via its action at pericytes. Data presented here identifies a novel potential role for pericytes in the acute renal failure observed in patients with acute pancreatitis.Research supported by BBSRC, Wellcome Trust and the MRC
Attenuated contractility in afferent arterioles during development of proteinuria in two‐kidney, one‐clip hypertensive rats
Authors: Dahl Tone Dolva , Skogstrand Trude , Helle Frank , Hultström Michael , Tenstad Olav , Iversen The late Bjarne Magnus 
Published: June 2021

AimsWe wanted to investigate the contractile properties of afferent arterioles (AAs) from two‐kidney, one‐clip (2K1C) hypertensive rats before and during development of proteinuria, and whether these vessels behave differently in outer and inner renal cortex.MethodsWistar rats were subjected to either a 2K1C or sham operation. Blood pressure was measured and urine was sampled before the rats were killed after 18 ± 4 weeks. AAs were isolated from outer and inner renal cortex of the non‐clipped kidney of the 2K1C and from both kidneys of the sham rats with the agarose infusion technique. The AAs were stimulated with angiotensin II (AngII) in increasing concentrations (10−10 M to 10−7 M), and degree of contraction was recorded.ResultsThe preliminary results are based on AAs isolated from 9 rats (Sham: 3, 2K1C without proteinuria (2K1C Prot−): 2, and 2K1C with proteinuria (2K1C Prot+): 4). There was no difference in mean arterial pressure between the 2K1C with and without proteinuria (184 ± 6 vs. 178 ±8 mmHg, NS).We found a significantly attenuated response to AngII 10−7 M in the superficial AAs from both hypertensive groups compared to sham. However, in the AAs from the juxtamedullary nephrons there was a preserved response in the vessels from the 2K1C rats without proteinuria.ConclusionLoss of contractile properties of AAs in deep cortex may contribute to development of renal damage and proteinuria in this model.
Renal ischemia‐reperfusion led to enhanced renal microvascular response to sphingosine‐1‐phosphate
Authors: Guan Zhengrong , Singletary Sean T. , Van Beusecum Justin , Cook Anthony K. , Inscho Edward W. 
Published: June 2021

Sphingosine‐1‐phosphate (S1P) potently vasoconstricts renal microvessels and participates in ischemia‐reperfusion (IR) induced acute kidney injury (AKI). We postulated that IR enhances renal vascular reactivity to S1P and contributes to AKI. Reactivity of juxtamedullary afferent arterioles (AA) to S1P was assessed in vitro in rats receiving 60 min bilateral ischemia followed by 24 hr reperfusion (B60IR) using the blood‐perfused juxtamedullary nephron technique (n=5–7/group). Plasma creatinine increased in B60IR (3.7±0.2 vs. 1.2±0.1 mg/dl in sham, p<0.05). Baseline AA diameter decreased in B60IR (11.8±0.7 vs. 14.6±0.6 μm in shams, p<0.05). S1P evoked concentration‐dependent AA vasoconstriction in both groups, however, the response was markedly enhanced in B60IR. S1P (10−10–10−5 M) reduced AA diameter to 93±1, 88±1, 76±1, 64±5, 46±5 and 35±4% of control in B60IR vs. 100±1, 94±2, 91±2, 81±4, 59±5 and 32±4%, respectively in shams. Conversely, AA responses to norepinephrine (NE) or KCl were unchanged. NE (10−8–10−6 M) reduced AA diameter to 92±2, 81±5 and 42±8% of control in B60IR compared to 92±2, 78±5 and 34±6% in shams. KCl (30, 60 and 90 mM) decreased AA diameter to 89±4, 51±6 and 40±7% in B60IR vs. 80±4, 38±4 and 32±4% in shams (p>;0.05). These data reveal that IR enhances AA reactivity to S1P and may contribute importantly to IR‐AKI.Funding sources: AHA10SDG3770010, DK44628 and HL074167
Glycogen Synthase Kinase‐3 Inhibition Reduces Renal Cystogenesis in Polycystic Kidney Disease
Authors: Rao Reena , Tao Shixin , Suderman Erin , Pandey Pankaj 
Published: June 2021

ObjectivePolycystic kidney diseases (PKD) are characterized by disregulated vasopressin (AVP) signaling in renal collecting ducts and elevated cAMP levels that contribute to progressive cyst enlargement. We previously found that inactivation of glycogen synthase kinase 3β (GSK3β) reduces AVP‐mediated increase in renal cAMP levels. Hence, we examined if inhibition of GSK3 could ameliorate cyst formation and growth in PKD.Methodscpk/cpk mouse model for autosomal recessive PKD show rapid postnatal renal cyst progression resulting in death by weaning. Wild type (WT) or cpk/cpk mice were injected daily with vehicle or GSK3 inhibitor, (TDZD‐8, 5mg/Kg BWt, IP) between postnatal days 3 to 14.ResultsGSK3β levels were elevated and detected in cyst‐lining epithelia of cpk/cpk mice. Renal cyst volume, kidney weight/ body weight ratio, blood urea nitrogen levels and interstitial fibrosis were significantly reduced in TDZD‐8 treated versus vehicle treated cpk/cpk mice. Renal cAMP levels were significantly reduced in TDZD‐8 treated cpk/cpk mice compared to vehicle treated cpk/cpk mice. In vitro cAMP induced cystogenesis assays revealed that GSK3 inhibitors like TDZD‐8 SB216763 and LiCl significantly reduces cyst formation by M1 cells.ConclusionThese studies show that inhibition of GSK3, a crucial kinase in AVP signaling preserves renal function in cpk/cpk mice by reducing renal cAMP levels and cystogenesis.
Blunting Circulating TH17 cells Decreases Hypertension and Oxidative Stress in Response to Placental Ischemia
Authors: Cornelius Denise C , Hogg James P , Wallace Kedra , Moseley Janae , LaMarca Babbette 
Published: June 2021

Preeclampsia (PE), new onset hypertension with proteinuria during pregnancy, is associated with chronic inflammation and placental oxidative stress (ROS). We have shown that chronic IL‐17 increases blood pressure and placental ROS during pregnancy. The objective of this study was to determine if TH17 blockade via IL‐17RC (recombinant receptor C) decreases hypertension and placental ROS in response to placental ischemia. On day 14 of gestation, mini‐osmotic pumps infusing 100 pg/day of IL‐17RC were implanted into pregnant rats undergoing RUPP (Reduced Uterine Perfusion Pressure). On gestation day18 carotid catheters were inserted and on day 19 blood pressure (MAP) was recorded, TH17 cells measured from peripheral blood leukocytes using flow cytometry, and placental ROS detected by chemiluminescence. One‐way ANOVA was used for statistical analysis. MAP increased from 101 ±3 mmHg in NP (n=18), to 118±4 mmHg in RUPP (n=21), decreased to 107±5 mmHg in RUPP+IL‐17RC rats (n=14). TH17 cells increased from 0.196 ± 0.1% in NP to 2.311 ± 1.2% in RUPP, and decreased to 1.003 ± 0.3% in RUPP+IL‐17RC rats. Placental ROS increased from 410 RLU in NP to 609 RLU in RUPP, but decreased to 511 RLU in RUPP+IL‐17RC rats. Infusion of IL‐17RC blunted TH17 cells, placental oxidative stress, and hypertension in the RUPP rat model of PE indicating that TH17 cell activation may play an important role in oxidative stress and hypertension during PE.This work was supported by NIH grants RO1HD067541 and T32HL105324
Sympathetic vascular transduction following spontaneous MSNA bursts is augmented in young black men
Authors: Credeur Daniel Paul , Holwerda Seth W , Fairfax Seth T , Keller David M , Fadel Paul J 
Published: June 2021

Young blacks exhibit an augmented vasoconstrictor response to α‐adrenergic agonists compared to whites. Whether this increase in α‐adrenergic receptor sensitivity in blacks evokes greater vasoconstriction to spontaneous bursts of muscle sympathetic nerve activity (MSNA) is unknown. Thus, in fourteen young normotensive black (N=7) and white men (N=7), MSNA (microneurography) and femoral artery blood flow (duplex Doppler ultrasound) were continuously measured for 20 minutes under resting conditions. Signal averaging was used to characterize beat‐by‐beat changes in leg vascular conductance (LVC) for 15 cardiac cycles following each individual MSNA burst. Variations in MSNA burst pattern (single vs. multiple successive bursts) and burst size (height) were considered. Blacks demonstrated a significantly greater reduction in LVC following single (blacks: −11.2±1.7 vs. whites: −4.6±1.24%; P<0.05) as well as multiple MSNA bursts (blacks: −19.4±2.0 vs. whites: −13.2±1.6; P<0.05). In addition, increases in burst height evoked graded reductions in LVC in both groups, with blacks having significant greater reductions in LVC. These preliminary findings suggest an augmented sympathetic vascular transduction in young normotensive blacks in response to spontaneous bursts of MSNA.Supported by NIH Grant R15HL096103 (DMK) and RO1 HL093167 (PJF)
Auditory and visual stimuli evoke a synchronised activation of sympathetic, respiratory and motor outputs after disinhibition of midbrain colliculi
Authors: Muller‐Ribeiro Flavia C.F. , Fontes Marco P. , Dampney Roger A.L. , Goodchild Ann K. 
Published: June 2021

The midbrain colliculi are involved in cardiovascular and behavioural responses to threatening stimuli. Disinhibition of this area can evoke spontaneous synchronized sympathetic and respiratory responses in anesthetized rats. This raised the question as to whether naturalistic stimuli can generate such responses. In urethane‐anesthetized, paralysed, vagotomised and artificially ventilated rats, abrupt sound (n=7) or bright light (n=5) generated synchronised bursts of activity in sympathetic (309 ± 30 or 217 ± 38%), phrenic (60 ± 18 or 43 ± 15 bpm), and sciatic (17 ± 4 or 15 ± 3%) nerve activities and blood pressure (30 ± 4 or 31 ± 8 mmHg) after disinhibition of ventral sites in superior and inferior colliculi. The onsets of the sympathetic, respiratory and sciatic responses following auditory or light stimuli occurred within a time period of <50 msec. Simultaneous multi‐sensory stimulation evoked an enhanced response. Blockade of the dorsomedial hypothalamus (DMH), dorsolateral periaqueductal grey (dlPAG) or cuneiform nucleus using muscimol did not affect the responses. Our findings show that neurons in the colliculi can generate synchronised cardiovascular, respiratory and behavioural responses triggered by a sudden auditory or visual stimulus. The output pathways from the colliculi do not depend on synapses within the DMH, dlPAG or cuneiform nucleus.Supported by NHMRC 1028183 and 570912 and by Capes.
Elderly blacks have a similar sympathetic neural responsiveness but greater pressor response to cold stress than elderly whites
Authors: Okada Yoshiyuki , Edwards Jeffrey , Jarvis Sara S. , Best Stuart A. , Meier Rhonda L. , Bivens Tiffany B. , Vongpatanasin Wanpen , Levine Benjamin D. , Fu Qi 
Published: June 2021

Muscle sympathetic nerve activity (MSNA) response to cold stress has been reported to be greater in young blacks than whites. We evaluated whether elderly blacks have greater sympathetic activation during cold stress than age matched whites. MSNA (microneurography), blood pressure (BP), and heart rate (HR) were measured during supine baseline, 2‐min cold pressor test (CPT), and 3‐min of recovery in 10 elderly blacks [age 65 ± 4 (SD) yrs] and 30 elderly whites (69 ± 7 yrs). Mean BP increased during CPT (P < 0.001), while it was greater in blacks than whites at 2 min of CPT (114 ± 21 vs 103 ± 13 mmHg, P = 0.042). HR increased during CPT (P < 0.001) without a group difference (72 ± 7 vs 65 ± 10 mmHg, P = 0.113). MSNA burst frequency, burst incidence, and total MSNA increased during CPT (all P < 0.001). None of these variables showed racial differences during baseline (burst frequency: 51 ± 12 vs 48 ± 10 bursts/min, burst incidence: 77 ± 16 vs 80 ± 15 bursts/100beats, and total MSNA: 781 ± 266 vs 759 ± 241 units) or CPT (63 ± 10 vs 61 ± 10 bursts/min, 88 ± 10 vs 93 ± 8 bursts/100beats, and 1311 ± 636 vs 1476 ± 720 units; all P >; 0.050). Thus, elderly blacks have a greater pressor response to cold stress than elderly whites, which is not attributable to sympathetic neural response. Other vasoconstriction systems (i.e., sympathetic vascular transduction and/or non‐adrenergic vasoconstrictor mechanisms) must be involved.Supported by NIH R01 HL091078.
An inverse relationship between testosterone and muscle sympathetic nerve activity: an investigation in lean healthy females
Authors: Madison Erin Elizabeth , Miner Jonathon Cory , Miner Jennifer Ann , Kaplan Paul F. , Minson Christopher Todd 
Published: June 2021

It has been documented that women with polycystic ovary syndrome (PCOS) have an elevated level of testosterone, which coincides with having an increased resting level of sympathetic activity, as measured by muscle sympathetic nerve activity (MSNA). However, there is a lack of research into the effect of moderate testosterone levels on sympathetic activity in lean, healthy females. In order to isolate the impact of testosterone in these women, the level of estrogen and progesterone were controlled via hormonal suppression in 8 healthy, lean women using a gonadotropin hormone antagonist (GnRHa) protocol. After four continuous days of estradiol and progesterone suppression, each subject came into the lab for testing of total testosterone level via blood sample, and MSNA via microneurography of the peroneal nerve. The study day testosterone level in these lean women ranged from 10.3 – 36.4 ng/dL, and the average burst frequency at rest was 2 – 22 bursts/min. A negative correlation was found between total testosterone levels and MSNA (R2=48.26, p=0.056). Although a positive correlation has previously been documented in women with increased levels of the hormone testosterone, this study showed a negative relationship between these two variables under normal ranges of testosterone.Supported by NIH Grant HL081671.
Promising applications of nano‐encapsulated (−) epigallocatechin gallate during adipogenesis in 3T3‐L1 cells
Authors: Bapat Priyanka Vinayak , Sun Ming , Wang Shu 
Published: June 2021

BackgroundOverexpression of thermogenic genes in white adipose tissue can ameliorate obesity. Many studies reported acute thermogenic effects of epigallocatechin gallate (EGCG) in white adipocytes. However, its low stability limits its therapeutic applications. Objective of this study was to synthesize biocompatible nanoencapsulated EGCG (Nano‐EGCG) to increase stability and enhance biological effects.MethodsStability of Nano‐EGCG at 37°C was measured using HPLC system. 3T3‐L1 cells were treated at differentiation and maturation with native and Nano‐EGCG at 10 μM. Triglyceride content in mature adipocytes was measured by an enzymatic method. The gene expression levels were measured using real‐time PCR.ResultsNano‐EGCG was more stable than native EGCG in vitro. Nano‐EGCG significantly (p<0.05) reduced triglyceride content in mature adipocytes as compared to EGCG. Moreover, when preadipocytes were induced to differentiate with Nano‐EGCG, the expression levels of peroxisome proliferator activated receptor gamma coactivator1‐alpha (PGC1α), and uncoupling protein family (UCP 1,2,3) were significantly increased as compared to native EGCG.ConclusionNanoencapsulation significantly increased EGCG stability. Nano‐EGCG at low concentrations significantly reduced triglyceride content in mature adipocytes and increased the expression of thermogenic genes during differentiation.Grant Funding Source: TTU research incentive funding
Nesfatin‐1 does not influence intracellular calcium concentrations in neurons of the nucleus of the solitary tract or the paraventricular nucleus
Authors: Mimee Andrea , Ferguson Alastair V. 
Published: June 2021

Nesfatin‐1 (nes‐1) is a neuropeptide which exerts potent effects on food intake, cardiovascular parameters, and the stress axis. Immunohistochemical studies have shown expression of nes‐1 in the nucleus of the solitary tract (NTS) and paraventricular nucleus (PVN). To date there is minimal data describing the mechanism of action of nes‐1 in the brain. Using whole cell patch clamp recordings, we have previously shown bath applied nes‐1(10 nM) influences the membrane potential of 63% of NTS and 71% of PVN neurons. Here, as a first step in investigating the mechanism of nes‐1 actions, we examined the effect of nes‐1 on intracellular Ca2+ concentrations ([Ca2+]i) in dissociated NTS and PVN neurons loaded with the Ca2+ indicator Fura2‐AM. Bath application of nes‐ 1 at 10 and 100 nM increased [Ca2+]i in 4% (n=75) and 3% (n=84) of NTS neurons, respectively, as assessed by a minimum 20% increase in the ratiometric value of [Ca2+]i. Furthermore, 9% (n=125) of PVN neurons showed an increase in [Ca2+]i in response to 10 nM nes‐1. Our findings show nes‐1 does not influence [Ca2+]i in NTS or PVN neurons. A large discrepancy also exists in the proportion of neurons reported as responsive to nes‐1 in our electrophysiological vs calcium imaging experiments, suggesting studies of nes‐1 effects on [Ca2+]i may not be an appropriate method of evaluating neuronal nes‐1 activation patterns or mechanisms of action.Funding: NSERC, FQRNT, HSFO.
Nesfatin‐1 influences the excitability of subfornical organ neurons
Authors: Kuksis Markus Arnis , Dai Li , Ferguson Alastair V 
Published: June 2021

Nesfatin‐1, a centrally acting anorexigenic peptide, is produced in several brain areas involved in metabolic function and has been implicated in appetite and thirst reflexes. The present study was thus undertaken to determine the specific role of nesfatin‐1 in appetite and thirst regulation mediated by the subfornical organ (SFO). We first used RT‐PCR and were able to confirm the presence of nesfatin‐1 in SFO. We then used whole‐cell patch clamp recordings to investigate the influence of nesfatin‐1 on the membrane potential of dissociated SFO neurons. Approximately 68.8% (42 of 61) of neurons tested showed a response to nesfatin‐1 (10 nM and 1 nM). Of the responding neurons, 50% depolarized by a mean depolarization of 10.6 ± 1.64 mV (n=21) and 50% hyperpolarized by a mean hyperpolarization of −8.8 ± 2.2 mV (n=21). No effect was observed at a concentration of 100 pM (n=3). This study has demonstrated that nesfatin‐1 has the ability to change the membrane potential of SFO neurons, and therefore can be identified as a potential modulator of SFO function.Supported by the Canadian Institutes of Health Research
Behavioral Profile Assessment in Offspring of Swiss MiceTreated During Pregnancy and Lactation with Caffeine.
Authors: Silveira Anderson Luiz Bezerra , Melo Roberto Laureano , Seara Fernando Azevedo Cruz , Almeida Cláudio Silva , da Rocha Fabio Fagundes , Santos Alex Sander Nunes , Marinho Bruno Guimarães , Reis Luís Carlos , Cortes Wellington Silva 
Published: June 2021

The objective was to assess the behavioral profile in offspring of Swiss mice treated during pregnancy and lactation with caffeine. For this purpose, two groups (n=6 each, and BW~35g) of female mice were treated during pregnancy and lactation by: tap water and caffeine solution at a concentration of 0,3mg/mL through oral route. The offsprings obtained, by completing 70 days of life, were underwent a behavioral battery test. Statistical analysis was performed by student t test and the different significance adopted was p<0.05. According to our results, it was not found any significant differences in the tail suspension and rotarod test as well. However, in elevated plus maze test, programmed animals had a lower percentage of entries in open arms (48.01±2.16 vs. 32.19±4.07, P<0.05) and higher number of entries in closed arms (15.57±3.13 vs. 12.77±2.31, P<0.05). Moreover, in the light‐dark box test there was significantly increase in number of transition in treated animals (23.00±1,03 vs. 29.46±1.796, P<0.05). In the meantime, in the von Frey test it was observed that programmed animals had a pattern hypernociception (p<0.0001). We can conjecture that caffeine treatment causes change in central adenosine signaling and, therefore, may have led a cytoarquitetonic alterations in limbic and cortical regions associated with anxiety‐like behavior and modulation of nociceptive responses.Support: FAPERJ & CNPq.
Perinatal exposure to low levels of carbon monoxide impairs neurobehavior in adult mice
Authors: O'Neill John Timothy , Kehl Margaret L , Johnson Kristopher P , Cravedi Kevin , Barry Erin S , Grunberg Neil E 
Published: June 2021

Maternal smoking is associated with several adverse neurological outcomes including increased risk for SIDS and attention deficit disorder. Perinatal exposure to carbon monoxide (CO) disrupts development of brain structures and associates with neurological disorders.OBJECTIVEto uncover age and sex differences in neurobehavioral phenotype of perinatally CO‐exposed mice. Pregnant mice were exposed to 0, 75, and 150 ppm of CO approximating levels found in smokers from embryonic day 0 until weaning. We utilized the Open Field Test (OFT), Acoustic Startle Response/Prepulse Inhibition (ASR/PPI), and the Neurobehavioral Severity Scale Revised (NSS‐R) to evaluate changes in neurological and behavioral functioning in rodents. Animals were evaluated at 14 and 60 days of life (do).RESULTSAt 14 do: (1) NSS‐R increased (0.33±0.22, 1.56±0.19 and 1.27±0.23 at 0, 75 and 150 ppm respectively) indicating decreased sensory‐motor function after exposure to CO, with females showing greater sensitivity; (2) males and females exposed to CO showed decreased startle with and without pre‐pulse.RESULTSat 60 do: (1) OFT‐horizontal activity decreased without sexual preference; (2) CO‐exposed animals showed some enhanced startle with PPI. We conclude that perinatal exposure to CO is associated with mild neurological impairment in 14 do mice that persists to 60 days.Funding: Flight Attendant Medical Research Institute
Identification of novel scleraxis gene targets in cardiac myofibroblasts
Authors: Bagchi Rushita , Roche Patricia , Schweitzer Ronen , Czubryt Michael 
Published: June 2021

Cardiac fibrosis is a significant clinical problem yet lacks effective therapies. We have shown that the transcription factor scleraxis is a key regulator of collagen 1α2 gene expression in cardiac myofibroblasts. We now identify novel scleraxis gene targets via gain‐/loss‐of‐function. Scleraxis over‐expression in primary cardiac myofibroblasts decreased the expression of matrix remodeling enzymes matrix metalloproteinases 9 and 11 and tissue inhibitor of metalloproteinases 3. Expression of the proteoglycans versican and decorin were decreased following scleraxis overexpression, yet we observed no change in decorin and a loss of versican in scleraxis null hearts. The expression of thrombospondin 4 and the myofibroblast marker α‐smooth muscle actin (αSMA) was increased by scleraxis overexpression and strongly down‐regulated in scleraxis null hearts, and may thus represent direct scleraxis gene targets. Our results show that scleraxis exerts wide‐ranging effects on extracellular matrix‐related gene expression, with the effect on αSMA expression suggesting that scleraxis may contribute to the fibroblast‐to‐myofibroblast transition that accompanies cardiac fibrosis, further supporting our general hypothesis that scleraxis represents a novel therapeutic target for this disease.Supported by the Canadian Institutes of Health Research & the St. Boniface Hospital Research Foundation.