bluuebunny/crossref_metadata_2025_split huggingface dataset:
Renal function and integrity are preserved when hydroxyethyl starch is dosed to acutely restore blood pressure after blood loss in rats
Authors: Patel Rohit , Fu Yiling , Huang Winnie , Freeman Brent , Honndorf Stefanie , Vallon Volker 
Published: June 2021

Hydroxyethyl starch (HES) is used clinically to replace blood loss and stabilize hemodynamics. However, the functional consequences on the kidney have not been fully investigated. Here we determine whether a single application of hydroxyethyl starch, dosed to restore blood pressure (BP) within minutes following a blood loss, affects kidney outcome when assessed one day or one week later.MethodsUnder short‐term anesthesia, Sprague‐Dawley rats were subjected to a 25% blood loss over 6.25 min via the femoral vein. Immediately thereafter, the Volulyte® 6% containing HES 130/0.4 (VOL) or Hextend® 6% containing HES 670/0.7 (HEX) or a balanced crystalloid solution (Isolyte®, ISO) were infused i.v. to restore BP within 4–4.5 minutes. Pilot studies established that this required doubling of the infused volume of ISO (20ml/kg) vs VOL and HEX (each 10ml/kg). Sham operated rats without blood loss/volume substitution were used as control (CON). Renal function was determined in renal clearance studies (using 3H‐inulin and paramino hippurate [PAH]) under terminal anesthesia. In separate groups of animals plasma and urine were collected and kidneys harvested for gene expression analysis. N=10–11/group.ResultsAs expected, hematocrit was significantly lower at 1 day after hemorrhage versus CON. The initial hematocrit drop at day 1 and the subsequent recovery after 1 week were similar in ISO, VOL and HEX. As indicated by similar values for body weight, blood pressure, plasma electrolytes, and hormone markers (including renin, ANP and ADH) among the 4 groups, the 3 volume substitution protocols rapidly restored the volume status at 1 day after hemorrhage and this effect was sustained 1 week later. The data also indicated that ISO, VOL and HEX similarly preserved renal hemodynamics (GFR, RBF), tubular reabsorption (Na, K, Cl, fluid, glucose, calcium, phosphate) and tubular secretion (PAH) at 1 day and 1 week after hemorrhage. Measurement of albuminuria and markers of kidney injury and inflammation (incl. urine NGAL to creatinine ratios and renal mRNA expression of KIM‐1, CCL2 and IL6) indicated that the level of injury or inflammation was not consistently increased among any of the 4 groups.ConclusionA single bolus infusion of ISO, VOL or HEX, dosed to acutely restore BP after a 25% blood loss in rats, preserved or maintained integrated kidney function to a similar extent, when assessed one day or one week later.Support or Funding InformationFresenius Kabi Deutschland GmbHThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Calcium Spark Activity is Modulated by Perfusion Pressure in Vascular Smooth Muscle of Afferent Arterioles
Authors: Yip Kay‐Pong , Balasuramanian Lavanya , Wang Lei , Liu Ruisheng , Ribeiro‐Silva Luisa , Sham James 
Published: June 2021

Myogenic response and tubuloglomerular feedback are the two primary mechanisms for renal blood flow autoregulation by regulating the afferent arteriolar vascular resistance. However, the mechanisms of mechanotransduction in pressure induced myogenic response are not well defined in afferent arterioles. We have previously demonstrated that integrin‐mediated mechanical force increases the occurrence of Ca2+ sparks in freshly isolated renal vascular smooth muscle cells (VSMCs). To test whether generation of Ca2+ sparks is a downstream signal of mechanotransduction in pressure induced myogenic constriction, the relationship between Ca2+ spark frequency and transmural perfusion pressure was investigated in intact VSMCs of afferent arterioles isolated from Sprague‐Dawley rats. Spontaneous Ca2+ sparks were found in VSMCs when afferent arterioles were perfused at 80 mmHg. The Ca2+ spark frequency was significantly increased when perfusion pressure was increased by 40 mmHg. Similar increase of Ca2+ spark frequency was also found when arterioles were stimulated with β1‐integrin activating antibody. Spontaneous membrane current recorded with whole cell perforated‐patch in renal VSMCs indicated that there were more spontaneous transient inward currents (STICs) than spontaneous transient outward currents (STOCs) when holding potential was set close to physiological resting membrane potential. These observations indicated that Ca2+ sparks activity might couple to Ca2+‐activated Cl− (ClCa) channel and trigger pressure induced myogenic constriction via membrane depolarization. Real‐time PCR and immunofluorescence confirmed the presence of the ClCa channel TMEM16A in renal VSMCs. Inhibition of TMEM16A with the specific antagonist T16Ainh‐A01 impaired pressure induced myogenic contraction in the perfused afferent arterioles. It is known that myogenic response is enhanced in spontaneously hypertensive rat (SHR). TMEM16A abundance and spontaneous Ca2+ sparks were more prevalent in renal arterioles of SHR than those of Sprague‐Dawley rats, which are consistent with notion that Ca2+ spark activity is part of the signal transduction process in myogenic response. In conclusion, Ca2+ sparks were detected in intact VSMCs of afferent arterioles for the first time and their frequencies were positively modulated by the perfusion pressure. The coupling Ca2+ sparks to ClCa might contribute to the mechanical signal transduction process in pressure induced myogenic constriction.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
BOWMAN'S CAPSULE CORRECTED: UNDISCOVERED VASCULAR CHAMBERS IN THE RENAL GLOMERULUS
Authors: Bates David O. , Arkill Kenton P. , Bell James S. , Winlove C Peter , Harper Steven J. , Neal Christopher R. 
Published: June 2021

The structure of the kidney glomerulus, known since Bowman's description in 18571, is of arterial afferent capillaries leading to exchange capillaries and an efferent arteriole. While investigating the three dimensional structure of the glomerulus we discovered that this description is incorrect in adult human glomeruli. Serial section reconstruction of glomeruli perfused‐fixed under physiological colloid osmotic and hydrostatic pressures showed that afferent and efferent arterioles lead into previously undescribed ellipsoid, wide vascular chambers (VCs). From the afferent vascular chamber (AVC), 5–7 long, non‐branching, conduit vessels lead to the glomerular edge where branching occurs. Using multiphoton microscopy, a signal consistent with banded (fibrilar) collagen was seen in second harmonic generation mode in unfixed glomeruli in a region consistent with vascular chamber walls imaged by two photon fluorescence. Electron microscopy confirmed that a layer of banded collagen surrounds VC walls. Approximately thirteen highly branched, first order vessels (E1) converge on the efferent VC (EVC), which drains into the efferent arteriole. Complex vortical flow modelling predicted that the AVC acts as a plenum manifold, distributing and balancing blood flow/pressure to conduit vessels supplying blood to different glomerular lobules. These previously undescribed adaptations of glomerular vascular structure in humans could regulate haemodynamic pressure and flow in glomeruli, and their disturbance provide a new mechanism to explain kidney diseases.Support or Funding InformationThe Richard Bright Research Trust, Kidney Research UK (2014–2015) and the Medical Research Council G10002073 and MR/K020366/1This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Time Course of Antioxidant and Vascular Function in Rat Aortas Following Acute, Exhaustive Exercise
Authors: Bucknor Morgan C. , Embry T. Hunter , Kling Divia D. , Jackson Jaren T. , Kodali Sruthi , Harris M. Brennan 
Published: June 2021

The purpose of this study was to examine the time course of changes in vascular reactivity and antioxidant status in rat aortas following an acute exhaustive bout of exercise. 7–9 mo old, male, Wistar rats were divided into four groups (n=9/group): sedentary (SED), 6 h post‐exercise (6 h), 24 h post‐exercise, and 48 h post‐exercise. Exercise consisted of one bout of exhaustive treadmill exercise lasting between 30–40 min. Endothelium dependent vasorelaxation was assessed in ring segments of the aorta by constructing an acetycholine (ACh) dose response curve (10−10–10−5 M) in a wire myograph.RESULTSMaximal vasorelexation was impaired in 6 h (67.7±5.4%) compared to SED (76.9±4.1%) and 24 h (80.2+5.5%). EC50 for ACh at 6 h (9.9±0.1e−7 M) was significantly (p<0.05) greater than SED (4.8±0.1e−7) and 24 h (3.9±0.1e−7). However, antioxidant capacity was not significantly (P<0.05) increased until 48 h post‐exercise (0.61±0.15 mM) compared to SED (0.14±0.05 mM). These data suggest that acute, exhaustive treadmill exercise results in impaired endothelial dependent vasorelaxation 6 h post‐exercise and returns and possibly improves within 24–48 h during which time antioxidant capacity is increased.Support or Funding InformationBorgenicht Program for Aging Studies and Exercise ScienceThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
ACUTE EXPOSURE TO NANO‐TIO2 PARTICLES CAUSES SEVERE ENDOTHELIUM‐ DEPENDENT DYSFUNCTION IN THE MIDDLE CEREBRAL ARTERY
Authors: Branyan Kayla D. , DeVallance Evan , Abukabda A , kelley Kelley , Nurkiewicz Timothy R. , Chantler Paul D. 
Published: June 2021

BackgroundThe use of engineered nanomaterials (ENM) is increasing; however, proper EMN toxicological assessments are typically incomplete. Previous studies demonstrate that ENM exposure is linked to adverse cardiovascular outcomes, including stroke. The cerebral microcirculation is key in regulating cerebral blood flow and any dysfunction may increase the risk of stroke. The direct impact of exposure to nano‐titanium dioxide (TiO2) on cerebral microvasculature is unknown.MethodsTo determine whether acute nano‐TiO2 exposure causes cerebral endothelial dysfunction, intratracheal instillation was used to deliver 240 μg of TiO2 suspended in 300 μl of sterile PBS vehicle to male and female Sprague‐Dawley rats 24 hours prior to surgery. The middle cerebral arteries (MCAs) were isolated and hung in a pressurized myobath. To assess endothelial‐dependent function, MCAs were challenged with increasing doses of acetylcholine (ACh; endo dependent dilation) and phenylephrine (PE; α‐adrenergic‐mediated constrictor). As endothelial dysfunction can be caused by oxidative stress, possibly through increased xanthine oxidase activity. To explore this, MCAs were incubated with Febuxostat (10 μM), a xanthine oxidase inhibitor, for 30 mins prior to treatment with Ach. To examine the effects of oxidative stress on MCA function we then exposed MCAs to the XO‐specific inhibitor, febuxostat (10 μM) for 30 min prior to ACh‐induced dilation.ResultsTiO2 exposure decreased MCA endothelium‐dependent dilation (p<0.05) in both sexes. However, febuxostat treatment restored the impaired dilation response in male rats, whereas no effect was observed in females. Interestingly, PE‐induced constriction of MCAs was also attenuated (p<0.05) in rats exposed to nano‐TiO2 compared to controls, suggesting overall MCA function was significantly decreased with nano‐TiO2 exposure.ConclusionThese data provide evidence that acute exposure to nano‐TiO2 significantly impairs MCA endothelium‐dependent dilation and constriction. However, incubation with a XO inhibitor limits this dysfunction but only in males, suggesting 1) a contributory role for XO in mediating TiO2 toxicity in the vasculature, and 2) an interesting sex‐related difference in the compromised cerebral microvascular health after nano‐TiO2 exposure. Experiments are underway to discover the underlying mechanism(s) that contribute to these observations.Support or Funding InformationNIH ES015022 (TRN); NIHGMS 1P20 GM‐109098 (PDC), AHA 16PRE30820000 (ED)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Augmented exercise pressor response during static handgrip in women with PTSD
Authors: Yoo Jeung‐Ki , Parker Rosemary S. , Anderson Elizabeth H. , Badrov Mark B. , Suris Alina M. , Fu Qi 
Published: June 2021

Post‐traumatic stress disorder (PTSD) is a psychiatric illness that is more prevalent in women than men, and there is growing evidence suggesting a clear link between PTSD and future development of cardiovascular disease. The underlying mechanisms are unclear, but enhanced sympatheticreactivity to daily stressors may be involved. We hypothesized that PTSD women would have an augmented vasomotor sympathetic response to static exercise. We measured heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) in 12 female patients with PTSD and 8 healthy women (controls) during static handgrip (SHG) exercise to fatigue at 40% of maximal voluntary contraction (MVC) force followed by 2 min of postexercise circulatory arrest (PECA) and 3 min of recovery. The total SHG time was divided evenly into five stages. Age, body mass index, and body surface area were not different between groups. MVC and the time to fatigue during SHG did not differ between patients and controls (P>0.05). MSNA burst frequency (BF) in response to SHG was greater in patients than controls (timexgroup interaction P=0.03, time P=0.0001, group P=0.04), but not during PECA. During the early stages of SHG, PTSD patients showed greater MSNA BF compared to controls [stage 1: 40±5 (SE) vs.19±7 bursts/min; P=0.02, stage 2: 45±6 vs.25±7; P=0.03, stage 3: 55±6 vs.30±7; P=0.02). MSNA BF responses during stage 4 and 5 were not different between groups (P=0.09 and P=0.1, respectively). Similarly, PTSD patients showed greater systolic blood pressure (SBP) compared to controls during early stages of SHG (stage 1: 144±4 vs.129±5 mmHg; P=0.02, stage 2: 149±4 vs.132±5; P=0.03, stage 3: 159±6 vs.138±7; P=0.03, stage 4: 166±6 vs.143±7; P=0.04) but not in the last stage (at fatigue; P=0.2). SBP was not different between groups during PECA and recovery. Diastolic BP and HR were progressively increased during SHG, reached peak at the last stage, and were comparable between groups. These results suggest that women with PTSD have an augmented exercise pressor response, which may be attributed to enhanced mechano‐ rather than metabo‐reflexes. However, the actual role of the muscle reflex in cardiovascular risk in PTSD remains to be elucidated.Support or Funding InformationThis study is supported by Harry S. Moss Heart Trust research funding STU 082016‐057This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Oral Contraceptives Attenuate Metaboreflex in Young Women
Authors: Asirvatham‐Jeyaraj Ninitha , Chantigian Daniel , Keller‐Ross Manda L. 
Published: June 2021

BackgroundSkeletal muscle afferent feedback (group III/IV) increases mean arterial pressure (MAP) and heart rate (HR) during exercise. Evidence suggests that oral contraceptive (OC) use can increase resting blood pressure. The influence of OC on MAP and HR when activating group III/IV afferents is unclear.ObjectiveTo determine if women taking OCs have greater cardiovascular responses to activating group III/IV afferents and if phases of menstrual cycle influence this response.MethodsTwelve women (means ± SD; 24±2 yrs, 7 taking OCs) attended two identical experimental visits, once during early follicular (low estrogen, days 1–4, LE) and once during ovulation (high estrogen, days 10–14, HE). Visits included 1) 3 min of rest and 3 min of passive knee flexion (HUMAC Norm, CSMI, Stoughton, MA) to activate the mechanoreflex and 2) steady state cycling (5 min) with bilateral post exercise circulatory occlusion (PECO) (2 min) of the vastus lateralis to activate the metaboreflex. Continuous noninvasive blood pressure (Nexfin, Edward Lifesciences, Irvine, CA) and a 3 lead ECG (AD Instruments, Coloroado Springs, CO) measured MAP and HR, respectively.ResultsResting MAP was similar in women taking OC (90±4 mmHg) vs. no OC (87±8 mmHg, p=0.24). Mechanoreceptor activation did not increase MAP (OC: 90±6 mmHg and no OC: 88±8 mmHg) or HR (OC: 64±7 bpm and no OC: 67±12 bpm, p<0.05) in either group. MAP and HR were similar in women during both LE and HE phases with mechanoreflex activation (p>0.05). Metaboreflex activation increased MAP in women not taking OCs (steady state 95±23 mmHg vs. PECO 105±24 mmHg). On the other hand, MAP decreased with metaboreceptor activation in women taking OCs (steady state 94±12 mmHg vs. PECO 89±16 mmHg, p=0.032). Resting HR was greater in women not taking OCs (136±11 bpm) vs. OCs (107±32 bpm, p<0.05). HR declined with metaboreflex activation in both OC and no OC group irrespective of LE and HE phase (p<0.05).ConclusionsAlthough mechanoreflex activation did not influence MAP for either group of women, women taking OCs had an attenuated MAP with metaboreflex activation. This is in contrast to evidence suggesting that OCs can increase MAP at rest and may indicate that during exercise OC use can be beneficial in lowering blood pressure in women.Support or Funding InformationNo funding to disclose.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Blood pressure responses to hindlimb arterial bradykinin injection are mediated by bradykinin 2 receptors in decerebrate rats
Authors: Rollins Korynne S. , Butenas Alec L. , Kempf Evan A. , Hopkins Tyler D. , Sanderson Bailey C. , Copp Steven W. 
Published: June 2021

Mechanical and metabolic signals associated with skeletal muscle contraction activate a reflex that increases blood pressure during exercise (i.e., the exercise pressor reflex). Bradykinin is one metabolite that has been found to play a role in activating the exercise pressor reflex and also contribute to the reflex's exaggeration in a rat model of simulated peripheral artery disease (PAD) induced by chronic femoral artery ligation. Specifically, bradykinin 2 (B2) receptor expression was found to be greater in rat dorsal root ganglia (DRG) tissue of “ligated” rats compared to the expression found in DRG tissue of rats in which the femoral artery was patent (i.e., “freely perfused”). Moreover, the hindlimb arterial injection of bradykinin reflexly increased blood pressure more in ligated rats than it did in freely perfused rats. We tested the hypotheses that, 1) HOE‐140 (5 μg/kg), a selective B2 receptor antagonist, would reduce the pressor response to bradykinin (0.5 μg/kg) injection in both ligated and freely perfused decerebrate, unanesthetized rats and 2) the magnitude of the reduction would be greater in ligated rats than in freely perfused rats. In five rats in which a femoral artery was ligated 72 hours before the experiment, HOE‐140 significantly reduced the pressor response to bradykinin injection (control: 23±2, post HOE‐140: 5±1 mmHg; p<0.01). In freely perfused rats, bradykinin injection evoked pressor responses in two rats and depressor responses in four rats. HOE‐140 reduced the magnitude of the pressor response (control: 16±7, HOE‐140: 4±2 mmHg, n=2) and the depressor response (pre: −22±5, post: −2±1 mmHg; p=0.02, n=4) in those experiments. We hypothesized that the depressor response in the freely perfused rats was due to the fact that hindlimb blood flow was not arrested during bradykinin injection and, therefore, the vasodilatory effects of bradykinin overwhelmed reflex‐mediated vasoconstriction. In four additional freely perfused rats in which a depressor response to bradykinin injection was initially observed (−31±8 mmHg), we subsequently tightened an iliac artery/vein snare to arrest the hindlimb circulation. Tightening the snare in this manner unmasked bradykinin injection‐induced pressor responses (9±4 mmHg). We conclude that hindlimb arterial bradykinin injection in ligated rats consistently produced a pressor response that was mediated by B2 receptors. In freely perfused rats, the divergent responses to bradykinin injection (i.e., pressor or depressor) were also B2 receptor mediated. B2 receptors may play a role in evoking the exaggerated exercise pressor reflex that is found in the rat model of simulated PAD.Support or Funding InformationSupported by University/Department funds.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Prolonged Leg Vasodilator Kinetics across an Exercise Transient in Older Adults
Authors: Hughes William E. , Kruse Nicholas T. , Casey Darren P. 
Published: June 2021

Aging is associated with attenuated exercise hyperemia at the onset of exercise as well as during steady‐state exercise. How these two exercise states are related, and whether age‐associated impairments at the onset of exercise carry‐over into steady‐state exercise are unclear. The purpose of this study was to examine leg vasodilator kinetics preceding steady‐state exercise, as well as examine whether kinetic responses are altered with aging. Sedentary to recreationally active young (n=9), and older adults (n=13) performed single and rhythmic dynamic leg contractions at 20% and 40% work‐rate maximum (WRmax). Femoral artery diameter and blood velocity were measured by Doppler ultrasound. Vascular conductance (VC; ml·min−1·mmHg−1) was calculated using blood flow (ml·min−1) and mean arterial pressure (mmHg). Single contraction responses were described by peak (magnitude) and total (volume) responses. Kinetic responses for VC were modeled using an exponential model, expressed as mean response time (MRT; duty‐cycles). Older adults exhibited reduced peak VC responses to single contractions relative to young adults at both 20% and 40% WRmax (P<0.05). There were no differences in VC MRT between older and young at 20% WRmax (P=0.49). Older adults exhibited prolonged VC MRT at 40% WRmax vs. young (37±4 duty‐cycles vs. 24±4 duty‐cycles; P<0.05). When matched for a similar absolute workload (~9W) older adults exhibited prolonged VC MRT relative to young (38±5 vs. 25±4 duty‐cycles; P<0.05). Peak responses to single contractions were inversely associated with MRT at 40% WRmax (r=−0.61; P<0.05) but not 20% (r=−0.02; P=0.94) or 9W (r=−0.10; P=0.67) in the group as a whole. Our data suggest 1) advancing age prolongs the kinetics of vasodilation leading up to steady‐state exercise at both relative and absolute exercise intensities; and 2) single contraction responses are inversely related to the kinetics of vasodilation preceding relative exercise intensity steady‐state exercise, perhaps indicative of a feed‐forward mechanism towards steady‐state.Support or Funding InformationFunded by NIH HL‐105467 (DPC)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.