bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thin Limbs of Henle and Inner Medullary Collecting Ducts are the Major Points of Flow Resistance Along the Renal Tubule
Authors: Gilmer Gabrielle , Deshpande Venkatesh , Schnermann Jurgen , Knepper Mark 
Published: June 2021

The driving force for flow along the nephron and collecting ducts is generally thought to derive from the pressure in the glomerular capsule (Bowman's space). In superficial nephrons of rats, the glomerular capsular pressure has been reported to be 12–13 mmHg under euvolemic conditions. To test the adequacy of this driving force, we calculated the theoretical pressure drop along each segment of the rat superficial renal tubule using the Hagen‐Poiseuille laminar flow equation with measured flow rates, tubule diameters, and tubule lengths. We used both a rigid tube model and an elastic tube model based on compliances from the literature. The rigid tube model predicted a net pressure drop from glomerular capsule to renal pelvis of 8.8 mmHg during antidiuresis and 15.5 mmHg during water diuresis. The latter value exceeds the measured value in the glomerular capsule. In contrast, the elastic tube model predicted a 9.5 mmHg pressure drop along the length of the renal tubule during water diuresis. In both models, the greatest flow resistance (pressure drop per unit length) was in the thin descending limb of Henle's loop and the final millimeter of the inner medullary collecting duct. We extended the elastic tube model during water diuresis to long‐looped nephrons (those with loops of Henle extending into the inner medulla). The predicted net tubular pressure drop for these nephrons was 18.3–20.3 mmHg depending on the location of the loop bend. The calculated overall flow resistance was higher in deep nephrons chiefly due to the thin descending and thin ascending limbs of Henle's loop. We do not have reliable glomerular capsular pressure values for deep nephrons. However, the glomerular capsular pressures in deep nephrons are unlikely to be substantially higher than in superficial nephrons because the single‐nephron glomerular filtration rate in deep nephrons is equal to or greater than in superficial nephrons. Thus, the calculated glomerular capsular pressure is 6–8 mmHg higher than the likely actual value with the elastic tube model. This leaves an apparent discrepancy that could be explained either by 1) an underestimate of the compliance of the thin limb segments of the long‐looped nephrons; or 2) an additional driving force for flow such as the peristaltic action of the renal pelvic contractions, which could boost the flow across the restriction points in the thin descending limbs and inner medullary collecting duct.Support or Funding InformationG.G. was a member of the 2017 NIH Summer Internship Program. V.D. was a member of the 2017 Biomedical Engineering Student Internship Program at the NIH.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Does obesity differentially impact male and female responses to skeletal muscle vasodilation during exercise?
Authors: Carter Katrina J. , Kellawan J Mikhail , Ward Aaron T. , Johansson Rebecca E. , Harrell John W. , Peltonen Garrett L. , Sauder Christina J. , Eldridge Marlowe W. , Schrage William G. 
Published: June 2021

BackgroundObesity increases risk of cardiovascular disease (CVD), and epidemiologic evidence suggests substantial sex differences in prevalence and burden of CVD. During dynamic exercise in healthy adults, we previously reported a more robust exercise vasodilator response in women compared to men. Therefore, we tested the hypothesis that obesity attenuates sex differences in exercise vasodilation. Obesity can reduce nitric oxide (NO) vascular signaling, thus we tested a second hypothesis that obese subjects exhibit lower NO‐mediated contribution to exercise vasodilation.Methods45 healthy lean young (18–40 year) adults (23 females; 22 males; BMI, 22 ± 2) and 26 obese young adults (16 females; 10 males; BMI, 37 ± 6) performed dynamic forearm exercise at 15% of maximal voluntary contraction for 10 minutes (20 contractions/min). Forearm vascular conductance (FVC) was calculated from forearm blood flow (FBF; Doppler ultrasound) and arterial pressure (brachial catheter), as FVC = FBF÷MAP. Lean forearm mass was determined (DEXA), and relative FVC (FVCrel; FBF • 100 mmHg−1 • 100 g−1 lean mass) was calculated. Baseline FVCrel was determined prior to exercise. Steady‐state exercise was reached within 2 minutes, and data were quantified from minute 4.5–5. Intra‐arterial infusion of L‐NMMA occurred from minutes 5–10 of exercise, and steady‐state data were quantified from minute 9.5–10. The change in FVCrel (ΔFVCrel) from baseline to steady‐state quantified the vasodilatory response to exercise, whereas the ΔFVCrel from steady‐state exercise to exercise+L‐NMMA quantified the contribution of NOS to exercise.ResultsResults are mean ± SD. Overall, women exhibited greater vasodilation (main effect for sex; ΔFVCrel, 18 ± 8 vs. 13 ± 6; p = 0.001). Furthermore, lean subjects exhibited greater vasodilation than obese subjects (main effect for group; ΔFVCrel, 17 ± 6 vs. 14 ± 9; p = 0.002). Contrary to the hypothesis, there was no sex‐by‐group interaction (p = 0.67). L‐NMMA infusion decreased steady‐state exercise FVCrel; but this response was not different by sex, obesity, or sex‐obesity interaction (p = 0.66).ConclusionsThese data indicate during dynamic exercise in young adults, exercise vasodilation: 1) is greater in females than males, 2) is reduced in obese compared to lean similarly between sexes, and 3) is mediated by a similar contribution of NO. Therefore, the differences observed in sex and group with steady‐state exercise are likely mediated by NO‐independent signaling.Support or Funding InformationHL105820, HL007936This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
NO/NOS‐Dependent Modulation of Inflammation in Acrolein‐Induced Vascular Toxicity
Authors: Brown Theresa , Joseph Mathew , Ranganna Kasturi , Xiao Daniel , Newaz Mohammad A. , Yousefipour Zivar 
Published: June 2021

Modulation of inflammatory signaling has been elucidated in different disease models including vascular biology. No/NOS system plays an important role in the process of inflammation. Balance between nitric oxide (NO) and superoxide is critical in inflammatory process. Peroxisome proliferator‐activated receptor gamma (PPARγ) has been implicated in pathology of diseases involving inflammation and in our previous studies we reported reduction in PPARγ protein expression and activity in animals exposed to acrolein. Since PPARγ influences both NO and superoxide generation, in this study we are proposing involvement of impairment of this regulation in acrolein‐mediated inflammatory response. Male iNOS knockout (inducible nitric oxide synthase, KO) mice were treated with acrolein (0.5 μg/kg; i.p.; 7 days) with/without rosiglitazone (Roz: PPARγ ligand, 10 mg/kg; orally; 10 days). Age/weight matched wild type (WT) were used as control. Urine and kidney tissue was processed for western blot and biochemical analysis. KO mice had higher (87%) 8‐Isoprostane in response to acrolein but lower NO (23%) compared to WT. Roz reduced 8‐isoprostane in KO mice by 47% and increased NO production by 35%. Total Antioxidant Status (TAS) was reduced in WT (31%) and KO (53%) mice treated with acrolein. Roz improved TAS in both KO (33%) and WT (21%) mice. Acrolein did not affect expression of eNOS (endothelial nitric oxide synthase) in WT and KO mice. Roz increased eNOS expression in WT (23%) and KO (33%) and iNOS expression in WT (28%). Expression of PPARγ was increased in WT (30%) and KO (28%) mice treated with acrolein and was further increased with addition of Roz (89% & 102% respectively). Based on these data, we are concluding that acrolein‐mediated reduction in PPARγ affects eNOS/iNOS/NO pathway and activation of PPARγ minimizes acrolein effect by improving PPARγ‐dependent NO/NOS interaction.Support or Funding InformationNIH, SC3GM103746This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Racial Differences in Forearm Vascular Conductance Response during Dynamic Handgrip Exercise
Authors: Barbosa Thales C. , Kaur Jasdeep , Stephens Brandi Y. , Akins John D. , Brothers R. Matthew , Fadel Paul J. 
Published: June 2021

Healthy young African‐Americans (AA) present impaired vasodilator function compared to Caucasian‐Americans (CA), as indicated by reduced flow‐mediated dilation, and lower vasodilation during mental stress. Whether such impairments affect vascular responses to dynamic exercise is unclear. Previous studies used relatively low‐intensity dynamic handgrip exercise, which resulted in a tendency towards lower forearm vascular conductance (FVC) and brachial artery blood flow (BABF) responses in AA as exercise intensity increased from 10% to 20% maximal voluntary contraction (MVC). Therefore, we hypothesized that with higher intensities, AA would present an attenuated increase in FVC to dynamic exercise. To investigate this, healthy young CA men [N = 6; 23 ± 2 years (mean ± SEM)] and AA men (N = 6; 20 ± 2 years) performed 6 trials of dynamic handgrip exercise at absolute workloads of 4, 8, 12, 16, 20, and 24 kg, while BABF (duplex Doppler ultrasound) and mean arterial pressure (MAP; finger photopletysmography) were continuously measured. FVC was calculated as: BABF/MAP. Each exercise trial lasted for 3 min with a duty cycle of 1‐s contraction/2‐s relaxation, with a minimum of 5‐min rest period between trials. Cadence was provided via metronome, with real‐time visual feedback of handgrip force. The groups had similar MVCs (CA: 56 ± 3 vs. AA: 53 ± 1 kg; P = 0.480), and the workloads used in the exercise trials represented an average of 7.4 ± 0.2%, 14.9 ± 0.4%, 22.3 ± 0.6%, 29.7 ± 0.8%, 37.1 ± 1.0%, and 44.6 ± 1.2% MVC. Both groups presented an intensity‐dependent increase in FVC. However, this FVC response was attenuated in the AA group (ANOVA interaction P = 0.046), with lower changes from BL at 8 kg (CA: +113 ± 10 vs. AA: +66 ± 10 mL min−1 100 mmHg−1; P = 0.025), 12 kg (CA: +152 ± 11 vs. AA: +89 ± 11 mL min−1 100 mmHg−1; P = 0.004), 16 kg (CA: +182 ± 14 vs. AA: +133 ± 14 mL min−1 100 mmHg−1; P = 0.020), and 24 kg (CA: +239 ± 21 vs. AA: +185 ± 21 mL min−1 100 mmHg−1; P = 0.011). Similarly, there was an intensity‐dependent increase in BABF in both groups, with a tendency of a lower response in the AA group (ANOVA group main‐effect P = 0.073). These preliminary findings suggest that, compared to CA, AA have an impaired vasodilator response to dynamic handgrip exercise.Support or Funding InformationSupported by UTA College of Nursing and Health InnovationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Vascular Function after Sauna Bathing in Healthy Older Adults
Authors: Gravel Hugo , Barry Hadiatou , Behzadi Parya Yousefi , Gagnon Daniel 
Published: June 2021

Repeated heat exposure by immersion in warm water improves vascular function in healthy young adults. This observation could explain the health benefits of sauna bathing reported in population‐based studies, in which regular sauna sessions lasting more than 19 minutes were shown to significantly decrease the risk of cardiovascular mortality. However, it is unknown if such sauna durations improve vascular function in older adults. The purpose of this study was to determine if 20 min of sauna bathing acutely improves vascular function in healthy older adults.Six older adults (4 women) without cardiovascular disease and risk factors (age range: 57–71 yrs) underwent a sauna bathing session consisting of 2 bouts of 10 min in a dry Finnish sauna (80°C) separated by 10 min of seated rest outside the sauna. Prior to and following sauna bathing, flow‐mediated dilation (FMD) of the brachial artery in response to reactive hyperemia induced by 5 min of forearm ischemia was assessed by Doppler ultrasound after a minimum of 30 min rest in the supine position in a quiet and thermoneutral environment. The percent change in artery diameter from baseline to peak was used as an index of macrovascular function, whereas post‐occlusive reactive hyperemia (PORH), estimated by the brachial artery flow area‐under‐the‐curve above baseline during the 3 min following ischemia, was used to evaluate microvascular function. Heart rate (HR), mean arterial pressure (MAP), oral temperature (Toral) and mean skin temperature (Tsk) were monitored throughout the study.Sauna caused an increase in HR (55 ± 8 to 86 ± 10 bpm, P<0.01), mean Tsk (33.0 ± 0.5 to 40.7 ± 0.7°C, P<0.01) and Toral (36.7 ± 0.3 to 37.4 ± 0.2°C, P=0.025) while changes in MAP were not statistically different (100 ± 8 to 90 ± 4 mmHg, p=0.137). At the time of FMD assessment, HR (53 ± 5 and 52 ± 5 bpm, P=0.56), MAP (92 ± 6 and 90 ± 5 mmHg, P=0.59) and Toral (36.8 ± 0.3 and 36.9 ± 0.1 °C, P=0.27) were similar before and after sauna bathing, whereas mean Tsk was elevated prior to the post‐sauna FMD assessment (34.3 ± 0.4 vs. 32.9 ± 0.5°C, P<0.01). FMD was similar before and after sauna bathing (4.79 ± 2.21% vs. 4.86 ± 2.73%, P=0.93). PORH was also similar before and after sauna bathing (286 ± 198 vs. 380 ± 168 ml, P=0.18).These preliminary results indicate that macro‐ and microvascular functions are unaffected by two 10 min bouts of sauna bathing at 80°C in healthy older adults.Support or Funding InformationFunded by Fondation de l'Institut de cardiologie de Montréal and by Fonds de Recherche du Québec – Santé.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Short‐Term Ingestion of Virgin Coconut Oil Improves Endothelial‐Dependent Dilation but not Exercise‐Mediated Hyperemia in Healthy Young Adults
Authors: Robinson Susan , O'Brien Myles William , Kimmerly Derek 
Published: June 2021

Virgin coconut oil (VCO) is high in antioxidants (e.g., polyphenols) that may reduce reactive oxygen species‐induced conversion of vascular endothelial‐derived nitric oxide (NO) to toxic peroxynitrite. As such, flow‐mediated dilation (FMD, a surrogate marker of NO bioavailability) and exercise‐mediated hyperemia may be enhanced following short‐term VCO supplementation. However, these potential beneficial effects have never been assessed in humans. We tested the hypotheses that a 4 week VCO supplement (30 ml·day−1) would improve resting popliteal artery (PA) FMD and the hyperemic response to aerobic exercise. Thirty‐four young, healthy participants were divided into VCO (n=19, 10♂, 22±2 years, 24±3 kg·m−2), and Control (n=15, 10♂, 24±2 years, 24±3 kg·m−2) groups. PA‐FMD and PA blood flow were assessed via high‐resolution duplex ultrasonography (Vivid i, GE Healthcare) and analyzed using commercial software (Cardiovascular Suite, Quipu). After resting measurements, a 10‐minute bout of moderate‐intensity (60% heart rate reserve) cycling exercise was completed. PA blood flow was measured for 5‐minutes post‐exercise and total PA blood volume was calculated from the area under the curve. After 4 weeks, PA‐FMD increased (p < 0.05) following VCO supplementation (4.9±0.9% to 5.5±1.2%) with no change (p > 0.9) in the Control group (5.7±2.1% to 5.8±1.9%). There were no differences (both, p > 0.28) in post‐exercise total PA blood volumes in either group (VCO: 495±355 ml to 598±384 ml; Control: 562±362 ml to 488±229 ml). The increased FMD response observed in our young healthy adults suggests that short‐term VCO supplementation has potential as a dietary treatment for populations with elevated ROS levels and reduced vascular endothelial (e.g., older adults, smokers, etc.). However, additional research is required to test this hypothesis.Support or Funding InformationSupport provided by: Canadian Foundation for Innovation: Leaders Opportunity Fund, and a Faculty of Health Professions Research Development grant. SAR and MWO were recipients of a NS Graduate Scholarship. MWO was awarded a NSHRF Scotia Scholar Award and a Heart & Stroke BrightRed Award.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Type 2 Diabetic Rats Develop Exercise Pressor Reflex Dysfunction Over Time: New Insight Into Aging With Diabetes
Authors: Grotle Ann‐Katrin , Huo Yu , Harrison Michelle L. , Graham James , Stanhope Kimber L. , Havel Peter J. , Fadel Paul J. , Stone Audrey J. 
Published: June 2021

Type 2 diabetes Mellitus (T2DM) patients have an augmented sympathetic activity and cardiovascular response to exercise. The exercise pressor reflex, which is evoked by mechanical and metabolic stimuli arising from contracting muscle, and results in an increase in mean arterial pressure and heart rate, may contribute to this augmented response. Studies have shown that the exercise pressor reflex is augmented in several cardiovascular related diseases including T2DM; however, it is not known how the exercise pressor reflex is expressed in aging T2DM rats. Therefore, the purpose of this study was to determine the expression of the exercise pressor reflex with aging in T2DM rats. We measured the exercise pressor reflex in unanaesthetized, decerebrated UC Davis T2DM rats and healthy (CTL) Sprague Dawley rats by statically contracting the hindlimb for 30 s while mean arterial pressure (MAP) and heart rate (HR) were continuously measured. Young (4 mo old) adult T2DM rats (BW: 594±15 g, glucose: 337±73 mg/dl, HbA1c: 7.4±0.3%) and older (12 mo old) adult T2DM rats (BW: 546±26 g, glucose: 549±28 mg/dl, HbA1c: 12.82±0.18%), were compared to adult CTL rats (BW:465±18 g, glucose: 200±14 mg/dl, HbA1c: 4.73±0.1%). We found that the pressor (younger T2DM: ΔMAP=21±5 mmHg, n=4; older T2DM: ΔMAP=39±5 mmHg, n=5; CTL: ΔMAP=17±2 mmHg, n=8; p<0.05) but not cardioaccelerator (younger T2DM: ΔHR=16±4 bpm, n=4; older T2DM: ΔHR=19±7 bpm, n=5; CTL: ΔHR=14±1 bpm, n=8; p>0.05) responses to static contraction were significantly greater in the older adult T2DM, but not in the younger T2DM rats compared to the CTL rats. Developed tension was similar for all group comparisons, p>0.05. We conclude that older T2DM rats develop an augmented exercise pressor reflex to static contraction of the hindlimb, but this hyper‐reactivity is not present in younger T2DM rats. In a population where exercise is typically prescribed as a treatment modality, an augmented exercise pressor reflex can put these individuals at a higher risk for experiencing cardiovascular events while exercising.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Blocking Interleukin‐6 Signal Pathway Attenuates Exaggerated Exercise Pressor Reflex in Rats with Femoral Artery Occlusion
Authors: Lu Jian , Xing Jihong , Li Jianhua 
Published: June 2021

A rat model of femoral artery occlusion was employed to study the exercise pressor reflex in peripheral artery disease. Prior studies have shown that pro‐inflammatory interleukin‐6 (IL‐6) is engaged in the amplified blood pressure response to static muscle contraction in occluded rats. IL‐6 complexes with soluble IL‐6 receptor (IL‐6R) to activate cells expressing the signal transducer glycoprotein (gp130). Thus, the current study was to determine the role played by IL‐6 activated signal complex (IL‐6‐gp130) in regulating the exercise pressor reflex in rats with femoral occlusion. Following 72 hours of femoral artery occlusion, the levels of protein expression of IL‐6R and gp130 were increased in dorsal root ganglion (DRG). In addition, we examined the pressor response to static muscle contraction after 62.5 ng/kg and 125 ng/kg of SC144 (a gp130 inhibitor) were injected into the arterial blood supply of the hindlimb muscle of control rats and occluded rats. We found that SC144 significantly attenuated the pressor response to contraction in occluded rats, but the effect of SC144 was not observed in control rats. In control rats, peak response of mean arterial pressure (MAP) was 15±2 mmHg after saline and 12±3 mmHg after 125 ng/kg of SC144 (n=6; P > 0.05 vs. saline). In occluded rats, peak MAP response was 25±5 mmHg after saline and 14±5 mmHg after 125 ng/kg of SC144 (n=6; P < 0.05 vs. saline). There was no difference in developed muscle tension between saline group and group injected with SC144 (528±28 g in saline control vs. 545±29 g with SC144 injection, P > 0.05). Overall, our data suggest that IL‐6 signal mechanisms in muscle sensory nerves contribute to the exaggerated sympathetic and pressor responsiveness observed during exercise in experimental rats with peripheral artery disease.Support or Funding InformationThis study was supported by NIH P01 HL134609This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Three days of chronic intermittent hypoxia is sufficient to induce β1‐adrenoceptor dependent increases in left ventricular contractility
Authors: Lucking Eric F. , Dhaliwal Pardeep , O'Halloran Ken D. 
Published: June 2021

Chronic intermittent Hypoxia (CIH) is the primary pathological feature of obstructive sleep apnea, manifesting sympathetic nervous system hyperactivity and hypertension. Modest durations of CIH exposure have been shown to increase cardiac output that may contribute to the hypertensive state. Prolonged CIH exposures induce heart failure. We sought to determine if increases in cardiac work develop before the CIH‐induced hypertensive phenotype is established.Male Wistar rats were exposed to repetitive cycles of hypoxia (FiO2=0.05 nadir; 90 seconds) and normoxia (FiO2=0.21; 210 seconds) for eight hours per day for three days (CIH; n=6). Sham animals (n=7) were constantly exposed to room air and the same environmental cues. Assessment of cardiovascular parameters was performed under urethane anesthesia (1.5 g/kg i.p.). Data are presented as mean±SD (sham vs CIH) and were analysed using unpaired Student's t‐tests. P<0.05 was taken as significant.Systolic blood pressure (p=0.439), mean arterial pressure (p=0.267) and heart rate (p=0.149) were all unaffected by three days of CIH exposure. In addition, plasma adrenaline (p=0.294) and noradrenaline (p=0.155) concentrations were not elevated in CIH exposed animals compared with sham controls. However, at baseline, left ventricular contractility (dP/dtMAX) was significantly increased in CIH exposed animals compared with sham animals (12320 ± 2725 vs 15300 ± 2002 mmHg/s; p=0.025). Interestingly, β1‐adrenoceptor inhibition with atenolol (5 mg/kg; i.v.) provided greater inhibition of left ventricular contractility in CIH animals compared with sham animals (−4747 ± 2080 vs −7604 ± 1298 mmHg/s; p=0.014), reducing dP/dtMAX to equivalent levels. Systolic blood pressure (p=0.735) and heart rate (p=0.25) responses to atenolol were similar in sham and CIH animals. Sympathetic ganglion blockade with hexamethonium (25 mg/kg; i.v.) produced equivalent responses in CIH and sham animals for measured cardiovascular parameters (p>0.05).This study suggests that global sympathetic hyperactivity has not yet developed in this three‐day model of CIH, as evidenced by catecholamine concentrations, blood pressure and heart rate, which are equivalent with sham animals. Nevertheless, three days of CIH exposure is sufficient to increase cardiac work. We hypothesize that through this mechanism the heart drives development of the hypertensive phenotype in the early stages of CIH, as opposed to sympathetically‐mediated peripheral vasoconstriction.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.