bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of aging on vasomotion responses to varying rates of local heating.
Authors: Del Pozzi Andrew T. , Martin Zachary T. , Soave Kayla M. , Hodges Gary J.
Published: June 2021

We compared the cutaneous microvascular vasomotion responses of 8 young (23 ± 1 yr) and 8 older (68 ± 2 yr) adults in the forearm and leg using laser‐Doppler fluxmetry (LDF) and wavelet analysis to investigate endothelial, neurogenic, and myogenic activity. We measured cutaneous microvascular responses at uncontrolled basal temperature (27 ± 2.2 °C), controlled basal temperature (33 °C), and initial vasodilation (onset of heating), and sustained vasodilation, at 42 and 44 °C, in response to both a slow (0.1 °C · 10 s‐1) and a fast (0.5 °C · 10 s‐1) local heating protocol. At baseline (no heating), there were no differences between the groups (all P > 0.05). At a controlled local temperature of 33 °C (thermoneutral), neurogenic activity was higher in the leg of the young compared to the older group (P = 0.04). Following the initiation of the heating protocols, the young participants responded with higher neurogenic activity in the forearm compared to the older group during fast local heating (P = 0.03), but not in response to slow local heating (P > 0.05). In the leg, the young group had higher endothelial nitric oxideindependent activity compared to the older group (P = 0.01) for both heating protocols. The young group also had an increase in endothelial nitric oxide‐dependent activity during the slow protocol (P < 0.001), while the older cohort experienced increases in neurogenic (P = 0.02) and myogenic (P = 0.04) activity. Following 35 min at 42 °C, neurogenic activity was significantly increased in the leg of the older group compared to the young group during the slow heating protocol (P = 0.02). Furthermore, after increasing local temperature from 42 to 44 °C, the older adults had higher endothelial nitric oxide‐independent activity (P = 0.04) in the forearm of the fast protocol while the young subjects had higher neurogenic activity (P = 0.04). Neurogenic activity in the leg of the older group was increased (P = 0.02) during the fast protocol at 44 °C. These results suggest that regional differences in the response to local heating persist with age and that the primary mechanisms responsible for vasodilation caused by local heating are diminished with age; however, overall vasodilation is offset by the other mechanisms. Moreover, our results suggest that as we age the reliance on endothelial activity shifts from endothelial nitric oxide‐dependent to endothelial nitric oxide‐independent mechanisms. These data suggest that the cutaneous bioavailability of nitric oxide is diminished with age.

Support or Funding Information

Ball State University SPA Fellows Stipend

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Critical role of angiotensin II type 2 receptors in the control of mitochondrial and cardiac function in angiotensin II‐preconditioned rat hearts
Authors: Nuñez Rebeca , Javadov Sabzali , Escobales Nelson
Published: June 2021

Angiotensin II preconditioning (APC) involves an angiotensin II type 1 receptor (AT1‐R)‐dependent translocation of PKCɛ and survival kinases to the mitochondria leading to cardioprotection after ischemia‐reperfusion (IR). However, the role that mitochondrial AT1‐Rs and angiotensin II type 2 receptors (AT2‐Rs) play in APC is unknown. We investigated whether pretreatment of Langendorff‐perfused rat hearts with losartan (L, AT1‐R blocker), PD 123,319 (PD, AT2‐R blocker) or their combination (L+PD), affects mitochondrial AT1‐R, AT2‐R, PKCɛ, PKCδ, Akt, PKG‐1, MAPKs (ERK1/2, JNK, p38), mitochondrial respiration, and cardiac function. The results indicate that expression of mitochondrial AT1‐Rs and AT2‐Rs were enhanced by APC 1.91‐fold and 2.32‐fold, respectively. Expression of AT2‐R was abolished by PD but not by L, whereas the AT1‐R levels were abrogated by both blockers. The AT1‐R response profile to L and PD was also shared by PKCɛ, Akt, MAPKs, and PKG‐1, but not by PKCδ. A marked increase in state 3 (1.84‐fold) and respiratory control index (1.86‐fold) of mitochondria was observed with PD regardless of L treatment. PD also enhanced the post‐ischemic recovery of RPP by 74% (p<0.05) compared with APC alone. Losartan, however, inhibited the rate pressure product (RPP) by 44% (p<0.05) before IR and reduced the APC‐induced increase of post‐ischemic cardiac recovery by 73% (p<0.05). These findings suggest that APC upregulates angiotensin II receptors in mitochondria and that AT2‐Rs have a permissive effect on AT1‐R‐dependent signaling and suppress mitochondrial respiration and cardiac function. These results support a critical role of mitochondrial AT2‐Rs in the control of cardiac function in APC.

Support or Funding Information

Supported by the National Institutes of Health (NIH) Research Centers in Minority Institutions (RCMI) Program grant No. G12M007600, National Heart, Lung, and Blood Institute (NHLBI) grant SC1HL118669 (SJ), and the University of Puerto Rico.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dopamine Receptor D3 Agonist (Pramipexole) Abolishes Morphine‐Induced Cardiac Fibrosis in Mice
Authors: Gaweda Gabriel G. , Iyer Rugmani P. , Shaver Patti R. , Grilo Gabriel A. , Dinkins Mai‐Lynne , Stoffel Hamilton J. , Clemens Stefan , de Castro Brás Lisandra E.
Published: June 2021

Prolonged morphine exposure leads to desensitization of the G protein‐coupled mu‐opioid receptor (MOR). Additionally, extended morphine exposure has been shown to associate with cardiac dysfunction. This is problematic for patients undergoing withdrawal from extended morphine pain management, especially those with pre‐existing heart conditions. Recent literature suggests mechanistic interactions between MOR and the dopamine receptor D3 (DRD3). The purpose of this study was to investigate whether a DRD3 agonist (pramipexole, 0.5 mg/kg/day, i.p.; DRD3ag) could reduce morphine‐induced cardiac dysfunction in mice. Thirty mice were randomly divided into 5 groups (G1–G5, Figure 1) and treated with morphine (2 mg/kg/day, i.p.) for 7 days (D7). Two groups were euthanized after morphine tolerance was established at D7 (G1, morphine only; G2, morphine + DRD3ag). The other 3 groups (D14) underwent a subsequent 7‐day period of morphine withdrawal (G3, withdrawal no treatment; G4, morphine + DRD3ag until D7 followed by withdrawal until D14; G5, morphine until D7 followed by withdrawal + DRD3ag until D14). Echocardiography was performed on each animal at D0 to establish a baseline for cardiac function, on D7, and again on D14. Histology and immunoblotting were conducted on the left ventricle (LV) to measure tissue fibrosis, myocyte hypertrophy, and DA receptor expression. Our data show that morphine treatment for 7 days followed by withdrawal induced cardiomyocyte hypertrophy and significantly increased myocardial fibrosis (both at D7 and D14). Picrosirius red staining showed that DRD3ag treatment completely abolished morphine‐induced fibrosis, independent of treatment time. Moreover, significantly decreased cardiomyocyte hypertrophy was noted in all groups receiving DRD3ag in the morphine withdrawal phase. Immunoblotting shows that morphine withdrawal significantly reduced DRD3 expression independent of the presence of DRD3ag. Our results suggest that using a DRD3ag as an adjunctive therapy with morphine could decrease morphine‐induced cardiac fibrosis, and subsequently blunt morphine‐dependent cardiac dysfunction. Further, our data suggest that the DRD3 agonist pramipexole has cardioprotective potential when administered during morphine withdrawal.

Support or Funding Information

The Brody School of Medicine Research Distinction Track, the Department of Physiology, and the Research and Graduate School at East Carolina University.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Inhibition of ICa,L by DHEA in Aortic Smooth Muscle Cells: Voltage‐dependency, Modulation by GPCR Signaling and Inhibition of Glucose‐6‐phosphate Dehydrogenase
Authors: Ochi Rikuo , Chettimada Sukrutha , Gupte Sachin A.
Published: June 2021

Dehydroepiandrosterone (DHEA) is a hormone abundantly released from adrenal cortex as DHEA‐sulfate (DHEA‐S). DHEA‐S is released also in brain. DHEA and epiandrosterone (EPI), a metabolite of DHEA, produces relaxation of high‐K+ induced contraction of aortic smooth muscle (ASM). EPI increases voltage‐dependent inactivation (voltage‐dependent inhibition, VDI) of ICa,L in ventricular myocytes. Whole‐cell ICa,L was recorded as IBa from ASM cells (ASMCs) of A7r5 cell line and enzymatically isolated bovine coronary ASMCs to study mechanism and modulation of DHEA‐induced inhibition of ICa,L. DHEA produced VDI; acceleration of time course of inactivation, increase of inhibition by depolarization of holding potential (HP) and leftward shift of steady state inactivation curve; f∞, 2s‐V, obtained by 2 s conditioning pulse and f∞, HP‐V as a function HP. In addition, DHEA produced voltage‐independent inhibition (VIDI) represented by inhibition of peak amplitude (ICa,L,peak) of ICa,L elicited by pulses from hyperpolarized HPs. Window ICa,L (IWD) supplies Ca2+ in the E‐C coupling of ASM. IWD obtained from I–V of ICa,L,peak and f∞, HP‐V fitted well with recorded IWD and they were strongly inhibited by DHEA. Efficacy of DHEA‐induced VDI was reduced by rightward shift of f∞, 2s‐V curve produced by depletion of cholesterol by MβCD. Blocking of GPCR signaling by intracellular dialysis of GDP‐β‐S also shifted f∞, 2s‐V to the right and it produced decrease of DHEA‐induced inhibition of ICa,L at depolarized HP (VDI). DHEA and EPI are inhibitors of glucose‐phosphate‐dehydrogenase (G6PD), a redox‐related pentose‐phosphate pathway enzyme. 6‐Aminonicotinamide (6‐AN), another inhibitor of G6PD produced VIDI without inducing VDI. DHEA‐S that does not inhibit G6PD induced small but significant VDI at an order higher concentration of DHEA without generating VIDI. GPCR signaling and membrane cholesterol are indirectly involved in the modulation of DHEA‐induced VDI by affecting basal voltage‐dependent inactivation. The occurrence of VIDI by 6‐AN indicates that G6PD inhibition underlies DHEA‐induced VIDI. DHEA‐induced inhibition of IWD by VDI and VIDI contributes for DHEA‐induced relaxation of ASM.

Support or Funding Information

National Heart, Lung, and Blood Institute Grant RO1 HL‐085352 to S. A. Gupte.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Yoda1‐induced phosphorylation of the Akt and ERK1/2 does not require Piezo1 activation
Authors: dela Paz Nathaniel G. , Frangos John A.
Published: June 2021

Piezo1 is a mechanosensitive cation channel that is expressed by endothelial cells (ECs) and can be activated by fluid shear stress. It has been previously shown to be important for a number of shear‐induced EC responses, ranging from increased intracellular calcium to cell alignment. Most recently, Piezo1 has been implicated as a critical regulator of vascular tone and blood pressure. Yoda1, a selective small molecule agonist of Piezo1, has been shown to induce responses similar to those activated by fluid shear stress in ECs, such as calcium influx. Since shear stress‐induced intracellular calcium release is known to cause activation of Akt and ERK1/2, we sought to determine whether Yoda1 stimulation of EC can lead to similar responses and whether they are Piezo1‐mediated. In this study, we show that Yoda1 can robustly activate both the Akt and ERK1/2 signaling pathways in ECs. Additionally, we found that the ion channel antagonists, gadolinium and ruthenium red, but not the specific Piezo‐blocking peptide, GsMTx4, effectively blocks Yoda1‐induced Akt activation. Taken together, our results suggest that despite Yoda1 being a selective Piezo1 agonist, Yoda1‐induced activation of these two independent signaling pathways is not entirely dependent on Piezo1 activation.

Support or Funding Information

This work was supported by NIH MERIT Award R37 HL040696 to J.A.F.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of BKCa Channels in Mesenteric Artery Vascular Smooth Muscle Tone of Diabetic Rats
Authors: HERNÁNDEZ‐GARCIA ANA PATRICIA , HERNÁNDEZ‐MÉNDEZ AURELIO , CHI‐AHUMADA ERIKA GUADALUPE , ALGARA‐SUÁREZ PAOLA , ESPINOSA‐TANGUMA RICARDO
Published: June 2021

High conductance calcium‐dependent potassium (BKCa) channels are broadly distributed in different tissues where their activity is regulated by depolarization and calcium. The BKCa channels are abundant in vascular smooth muscle and their role regulating contractile tone has been widely discussed. Several studies have reported that in diabetes mellitus (DM) potassium currents mediated by these channels are diminished, especially in those located in small resistant vessels. BKCa channels are present in conducting arteries as well but their role in muscle tone seems to be small if any.

The objective of this work was to study the role of BKCa channels in muscle tone of diabetic rat mesenteric arteries.

Male Wistar rats (190 ± 10 gr in weight) were used and DM was induced by injecting streptozotocin (65 mg/kg) into de caudal artery. At 4, 8 and 10 weeks after streptozotocin or vehicle injection, rats were sacrificed and the mesenteric artery excised. We conducted isometric tension experiments using 10 micromolar of the selective channel activator NS1619 or 100 nM Iberiotoxin, a specific blocker of the BKCa channels applied at the peak of the maximum contraction induced by 10 microM phenylephrine (PE). We also took confocal fluorescence images to identify the localization of the alpha subunit ‐BKCa channel in mesenteric artery rings.

Tension experiments show that NS1619 had no significant effect on the contraction induced by PE neither in control or DM rats, no matter the time of DM evolution (for example, at 10 weeks the percentage of relaxation was of 11.93 ± 4.73 in DM and of 9.0 in control group). Similarly, Iberiotoxin by itself had a weak contractile effect on the vascular tone of control and DM groups (for example, DM of 10 weeks the percentage of contraction was of 2.65 ± 1.89 and of 6.07 ± 3.34 in control rats). Immunofluorescence shows that BKCa alpha subunit channel is present within the endothelium, the smooth muscle cells and the adventitia. However, it is noteworthy that the alpha subunit is more abundant in endothelial cells and to a lesser extent in muscle cells where it can be seen mainly at the cytoplasm.

We concluded that in spite that the BKCa channels are expressed in mesenteric artery smooth muscle, they do not participate in maintaining the muscle tone because they are present mainly intracellulary. At present we are conducting experiments to know the localization of the BKCa beta subunit and see if DM affect it.

Support or Funding Information

Supported by CONACYT Grant 223350 to RET

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Analysis of mutations in Muscle LIM Protein associated with human heart failure
Authors: Boateng Samuel , Atkins Jennifer , Hawanatu Sesay , Sorensen Thomas , McGuffin Liam
Published: June 2021

Heart failure is defined as a progressive condition in which the heart is unable to pump enough blood to meet the body's needs for oxygen and nutrients. A common cause of heart failure is due to genetic mutations in cytoskeletal proteins required for contractile activity and/or mechanosensing. These include proteins such as CSRP3 or muscle LIM protein (MLP) and a number of these mutations result in cardiomyopathy, heart failure and sudden death.

MLP is a small protein comprised of 194 amino acids and is found in the Z‐disk of the myofilaments in cardiac myocytes. MLP functions as a signalling molecule linking mechanosensing with cellular growth and adaptation. MLP can also interact with numerous proteins in the cytoplasm and nucleus. There are 5 key mutations in the MLP gene that can lead to cardiomyopathies. We investigated the L44P, S54R‐E55G, C58G, K69R and G72R mutations.

The aim of this investigation was to determine how these mutations elicit their effects by examining protein structural changes and effects on binding partners. The analysis was performed using bioinformatics tools and online servers.

The full length wildtype MLP sequence was submitted to a variety of servers along with the mutations. The results showed that L44P and C58G to have the most deleterious effect on the protein structure and function. G72R results in a stabilisation within the site directed mutator server, while K69R shows little effect. However, the G72R is likely to affect the nuclear localisation signal function thereby impairing its nuclear activity. We have previously shown that nuclear translocation of MLP is required for stretch dependent cellular adaptation in cardiac myocytes.

Radius of gyration and root‐mean‐square deviation of atomic positions plots indicate a more compact and less flexible protein with the L44P mutation compared with the wildtype. This would change the protein's sensitivity to mechanical stress thereby affecting downstream signalling and subsequent cellular remodelling.

Finally we examined the effect of the mutations on protein‐protein interactions with binding partners. All the mutations inhibited interactions with alpha actinin‐2 and cofilin while L44P, S54R‐E55G, C58G and G72R all prevented interaction with NRAP and TCAP. These interactions are essential for mechanosensing within the myofilaments or downstream signalling required to elicit an effective cellular response. This analysis gives a better understanding of the molecular function of MLP and how these mutations result in maladaptation and heart failure in man.

Support or Funding Information

Diamond Light Source Ltd and the University of Reading

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Nuclear‐mitochondrial crosstalk in the heart during diabetes mellitus – the impact on RNA in mitochondrial subpopulations
Authors: Hathaway Quincy Alexander , Shepherd Danielle Lee , Durr Andrya Jean , Hollander John Michael
Published: June 2021

The cellular milieu of diabetes mellitus, with changing substrate utilization, ROS, inflammation, and other factors, influences the function of the mitochondrion, which plays a vital role in bioenergetics. How the mitochondrion functions is affected both by the import of nuclear‐encoded mitochondrial proteins and by regulation of RNA transcripts within the mitochondrion. We have previously shown during diabetes mellitus, that pathways involving protein (HSPA9) and small RNA (PNPase) import are directly impacted. The implications of epigenetic control of the genome, which is shown to be globally altered in the diabetic heart, is relatively unexplored in regards to mitochondrial health and function. Type 2 Diabetic and non‐diabetic human right atrial tissue and db/db mouse whole heart were used for evaluation of epigenetic modifications to nuclear‐encoded mitochondrial proteins involved in protein and RNA import into the mitochondrion, HSPA9 and PNPT1, respectively. Also, analysis of human atrial mitochondrial RNA was examined. The promoter region of HSPA9 and PNPT1 were processed for histone activation/repression (H3K4me3 and H3K27me3, respectively) and DNA methylation. Chromatin‐immunoprecipitation qPCR evaluated differentially bound regions of H3K4me3 and H3K27me3. Bisulfite treatment, methylation PCR, and cloning were used to measure methylation status of CpG islands. Small RNAs were sequenced through NextGen sequencing for mitochondrial subpopulations, subsarcolemmal (SSM) and interfibrillar (IFM). During the diabetic pathology, HSPA9 was shown to have increased H3K27me3 association in human and mouse (P ≤ 0.05), while PNPT1 exhibited significantly lower H3K27me3 (P ≤ 0.05) and higher H3K4me3 (P ≤ 0.05) association in human and mouse. Neither gene had differential methylation patterns during type 2 diabetes mellitus. In type 2 diabetes mellitus, all human mitochondrial transcribed RNA transcripts had a significant decrease in expression in the SSM (Padj ≤ 0.05), while no changes in the IFM were observed. Our results suggest that during type 2 diabetes mellitus, nuclear‐encoded proteins that comprise the mitochondrial proteome and are involved in protein and RNA import can be epigenetically altered. Mitochondrial subpopulations also differentially express RNA during diabetic insult, with the SSM being more detrimentally impacted. Epigenetic alterations, and changes in RNA, reveal how environmental changes to the nuclear genome could shape mitochondrial structure and function.

Support or Funding Information

(Support: NIH R01 HL128485; AHA 17PRE33660333)

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
MODULATION WAY CLASSICAL AND ALTERNATIVES OF RENIN ANGIOTENSIN SYSTEM (RAS) IN MESANGIAL CELLS AFTER EXPOSURE TO FRUCTOSE.
Authors: Yokota Rodrigo , Jara Zaira Palomino , Matsumoto Larissa Emi , Aragao Danielle Sanchez , Casarini Dulce Elena
Published: June 2021

Background

Our group demonstrated previously that rats subjected to a high fructose diet showed increased activity of kidney ACE. In order to understand the effect of fructose in the forming process of angiotensin II (Ang II) and angiotensin 1–7 (Ang1–7) affecting the levels of these effectors, the aim of this study was to evaluate the activities of the RAS enzymes responsible for the formation of Ang1–7 and Ang II of immortalized human mesangial cells (IMCH)exposed to low and high concentration of fructose.

Methods

IMCH were divided into control (low glucose medium), Fructose 5 mM(medium + 5 mM Fructose) and Fructose 30mM(medium + 30 mM Fructose) groups. The enzymatic activity of ACE, chymase, cathepsin D, Neutral Endopeptidase (NEP) and ACE2 were evaluated using Z‐Phe‐His‐Leu, Abz‐AIKFFSAQ‐EDDnp, Abz‐AIAFFSRQ‐EDDnp, Abz(d)‐Arg‐Gly‐Leu, Mca‐APK (DNP) as substrates, respectively. Data were analyzed using ANOVA one way.

Results

Among the AngII forming enzymes, fructose decreased ACE activity (CG:0,044±0,01 vs.F5:0,016±0,004* vs. F30:0,008±0,002* mU/mg protein) in cell lysate. Both fructose concentrations increased chymase (CG:0,85±0,03 vs. F5:1,07±0,07* vs. F30:0,99±0,05* nM/min/mL) in the culture medium. No effect was observed on the activity of cathepsin D. When evaluating the activities of peptidases forming Ang‐1–7, NEP activity was decreased in lysate cells in F30 group and decreased in F5 group in culture medium. We did not detect differences in ACE2 activity.

Conclusion

The results suggest fructose modulates renal and systemic RAS in IMCH acting in the classical and alternative pathways of Ang II formation. Additionally, this sugar was able to decrease NEP activity, forming Ang‐1–7. Quantitation of angiotensin remains necessary to better understand how the end effector is available in IMCH and to evaluate possible effects on glomerular physiology.

Support or Funding Information

Capes

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Yoga based cardiac rehabilitation on Vascular and Endothelial function in patients post myocardial infarction – A randomized controlled trial
Authors: Christa S. Edmin , Jaryal Ashok Kumar , Yadav Raj Kumar , Roy Ambuj , Chandran Dinu S. , Deepak Kishore Kumar
Published: June 2021

Background

Vascular and Endothelial dysfunction is an independent predictor of cardiovascular and all cause mortality. We tested the effect of 12‐week Yoga‐based cardiac rehabilitation program on Vascular and Endothelial function in patients following acute myocardial Infarction

Methods

In this study, 80 patients (50.06 ± 9.43 years) were randomly assigned to either Yoga based cardiac rehabilitation group (YG) or Standard care group (CG) post acute‐myocardial infarction (MI). The YG received a structured yoga based cardiac rehabilitation program in addition to usual care. CG participants received three brief educational sessions. Baseline (at 3 weeks post MI) and post intervention assessments included carotid‐femoral pulse wave velocity (cf‐PWV), augmentation index (AIX@HR75) normalized to heart rate and flow mediated dilation (FMD). All recordings were done in the Autonomic & Vascular function lab, Department of Physiology at AIIMS, New Delhi (CTRI/2017/09/009925).

Results

Values are expressed as mean change score. After 12 weeks, no significant changes were found between groups in cf‐PWV(−0.29±2.18 vs. −0.18±1.70, p=0.82). AIX@HR75 decreased (0.35±5.08 vs. 3.88±8, p=0.02) and FMD increased (2.72±5.49 vs. −0.14±4.81, p=0.01) significantly in YG than the control group. Per‐protocol analysis (n=52) also provided similar results. There was no significant changes were found between groups in cf‐PWV(−0.84±2.90 vs. −0.12±1.89, p=0.40). AIX@HR75 decreased (−0.85±4.29 vs. 2.13±7.13, p=0.05) and FMD increased (3.36±6.38 vs. −0.28±5.22, p=0.02) significantly in YG than the control group.

Conclusions

Yoga based cardiac rehabilitation improved endothelial function and functional measure of arterial stiffness significantly. There was no significant change in structural measure of arterial stiffness. This signifies that short term yoga based rehabilitation could improve only the functional measures and may be insufficient to elucidate structural changes over 12 weeks.

Support or Funding Information

AIIMS, New Delhi, IndiaICMR, New Delhi, IndiaMRC, UK

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Resistance Training on Antioxidant Expression in Type I Muscle from Doxorubicin Treated Rats
Authors: Ahn WonMo , Hydock David Scott , Twaddle Mackenzie , Tigner Allison , Wagner Meghan , Bredahl Eric
Published: June 2021

The purpose of this study was to determine the effects of resistance training prior to and during doxorubicin (DOX) treatment on antioxidant enzyme expression in the primarily type I soleus muscle. Thirty‐six male, Sprague‐Dawley rats were randomly assigned to one of four groups: sedentary+saline (SSS), sedentary+DOX (SSD), resistance training+saline (RRS), and resistance training+DOX (RRD). The resistance training protocol incorporated a raised cage model where food and water were elevated progressively which provided hindlimb loading 10 weeks prior to DOX injection and during the course of DOX treatment. Animals receiving DOX received 3 mg/kg DOX administered i.p. weekly for 4 weeks (12 mg/kg cumulative). Five days following the final DOX injection, solei were excised and Western blotting was performed to quantify superoxide dismutase (SOD)1 and SOD2 expression. No significant main activity or drug effects were observed with SOD1 or SOD2 expression, but a significant activity × drug interaction was observed for SOD1 expression with RRD expressing significantly higher SOD1 than SSD. This interaction, however, was not observed for SOD2. In conclusion, resistance training prior to and during weekly DOX administration promoted an increase in SOD1 expression (the cytosolic form of SOD) suggesting that resistance training may play a role in combatting DOX myotoxicity by enhancing cytosolic antioxidant defenses.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Body weight influences genes related to energy metabolism in human skeletal muscle
Authors: Wu Hexirui , Dridi Sami , Ferrando Arny A. , Kim Il‐Young , Wolfe Robert R. , Baum Jamie I.
Published: June 2021

Over one third of adults in the United States are obese. Skeletal muscle is a major site of metabolic activity and the most abundant tissue in the human body. For skeletal muscle to function at optimal levels, the efficient activation of processes that regulate muscle development, growth, regeneration and metabolism is required. Mitochondria play a key role in ensuring adequate levels of ATP needed for skeletal muscle contraction. In addition, the capacity of skeletal muscle to contribute to whole‐body energy expenditure is related to the fact that muscle makes up ~40% of total body mass and accounts for 20–30% of total resting oxygen uptake. This indicates that mitochondrial functional capacity is likely to directly affect muscle metabolic function and have a significant impact on whole‐body metabolism. Mitochondria are also important for ensuring muscle is able to modulate substrate oxidation (e.g. lipid and carbohydrate oxidation) following a meal. The objective of this study was to determine if there was an effect of body weight on genes related to mitochondrial function in skeletal muscle from normal weight (NW) and obese/overweight (OW) participants. Muscle biopsies were taken from OW (n=31, ages 48±19) and NW (n=12, ages 43±18) adults. Gene expression was measured using real‐time PCR. There was an increase (p<0.05) in the expression of both PGC1α and PPARγ, which are regulators of mitochondrial biogenesis, in OW vs NW participants. Expression of UCP2, a key regulator involved in ATP synthesis, was higher (p<0.05) in OW participants. In addition, genes related to mitochondrial respiration, mitochondrial DNA replication and transcription, NRF1 and Tfam, had higher (p<0.05) expression in OW. Cpt1a, a gene encoding carnitine palmitoyltransferase 1A, which is necessary for fatty acid oxidation, had lower (p<0.05) expression in OW compared with NW. Conclusively, these data provide a preliminary view of differences in energy metabolism gene expression in obese/overweight versus normal weight individuals.

Support or Funding Information

Arkansas Biosciences Institute

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Characterizing Heat Stress and Strain in Electric Utility Workers by Means of a Questionnaire
Authors: Kenny Glen P. , Flouris Andreas D. , Brosseau Lucie , Dervis Sheila , Notley Sean R.
Published: June 2021

In recent field work we showed that the high physical demands combined with restrictions to heat loss due to protective work uniforms caused some electric utility workers to experience dangerous levels of hyperthermia (J Occup Environ Hyg. 2015;12:708). These findings indicate that heat stress in the electric utility industry may be detrimental to worker health and safety. In the present study, 414 workers in the power generation and delivery industry across 15 US states completed a two‐part on‐line questionnaire anonymously. Part 1 comprised 15 general questions on the worker's age, sex, role in the organization, general duties, workplace location, work shift duration, years of experience, level of physical activity, frequency of heat exposure, other. The second part consisted of a validated questionnaire for the assessment of heat stress at the workplace – the ‘Heat Strain Score Index (HSSI)’ (Int J Prev Med 2013; 4:631). It was composed of 18 questions which included key factors in heat stress evaluation (environmental parameters, work intensity, level of heat exposure, clothing insulation and permeability, etc.) and indicators of heat strain (sweat rate, fatigue, thirst, symptoms of heat‐related illness, etc.) with cut‐off scores as follows: ≤13.5, green zone or safe level; 13.6 to 18.0, yellow zone or alarm level; >18.0, red zone or danger level. The average (±SD) age of the respondents was 46(10) years and they reported being in their present position for 11(10) years. They typically performed 5(1) consecutive days of work lasting 10(6) hours each day. For all job types (all workers), 79% of respondents reported heat stress was a problem. This number was greater (93%) in those performing physically demanding jobs (e.g. linesman). Further, 30% and 67% of all workers indicated they were exposed to heat stress occasionally and daily, respectively. In contrast, 81% of linesman reported being exposed to heat stress on a daily basis with only 19% experiencing occasional exposure. Based on the HSSI, 43% of all workers and 68% of linesman were categorized in the red zone (danger level) and therefore at an elevated risk of a heat‐related injury (both p<0.01). Our findings demonstrate that electric utility workers are likely to experience excessive heat strain and research must be conducted to explore methods to effectively and efficiently manage heat stress and strain in these workers.

Support or Funding Information

Human and Environmental Physiology Research Unit (G.P. Kenny).

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Exercise effects on Thermoregulation in Obese Mexican Young Women
Authors: Garcia‐Pelagio Karla , Ambrosio Natalia , Espinoza Beda , Galicia Eugenio , Mejia Jorge , Navarro Luz
Published: June 2021

Obesity has become a serious global health problem affecting both adults and children that remains unclear. Mexico is one of the countries with the highest rate of obesity worldwide. As a disease, obesity has deleterious effects on metabolic homeostasis associated with increased heat production; however, subcutaneous adipose tissue provides an insulating layer that impedes heat loss. To maintain normothermia, obese individuals must increase heat dissipation. We explore the potential role of external and core temperature in energy balance, and develop the hypothesis that basal temperature and changes in the temperature response in various situations to the enhanced metabolic efficiency of the obese state. 45 participants divided in Normal (N), overweight (OW) and obese (O) young women out of the ovulatory state performed bicycle exercise for 15 min in a climatic chamber at 38°C previous acclimatization period. Skin and core temperature, cardiac frequency, arterial pressure and oxygen consumption were measured every 2 minutes before, during and after the exercise reaching the initial temperature value. Our results indicate an important increase in core temperature for OW and O population compared to N women. External temperature was higher in N women compared to OW and O. Notably; N women reach its initial temperature 3‐fold times quicker than O and OW women. Our data suggest a compelling evidence for a thermogenic handicap in the obese Mexican population.

Support or Funding Information

Supported partially by UNAM (PAPIIT IA207818) to KPGP

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
TRPV1 receptor antagonist blunts cholinergic‐mediated sweating
Authors: Mack Gary W. , Kunz Kevin R.
Published: June 2021

Cholinergic‐mediated primary sweat production requires an increase in Ca++ influx across the epithelial cell membrane of the sweat gland. Several Ca++ channels have been proposed to contribute to the increase in Ca++ influx. We tested the hypothesis that the nonspecific cation channel associated with the TRPV1 receptor, which are located on sweat gland epithelial cells, contributes to the Ca++ influx and thereby local sweat production. We measured local sweat rate (SR) with a 0.7 cm2 capsule placed on the skin overlaying an intradermal microdialysis probe used to deliver 20 mM capsazepine, a TRPV1 receptor antagonist, to the skin in 12 healthy young adults. Two small stainless steel needles were place into the skin (7 mm apart, 2 mm deep) and stimulated at a constant current intensity of 2.5 mA for 30 s at frequencies of 0.2, 1, 2, 4, 8, 16, 32, and 64 Hz to generate a sigmoidal shaped stimulus‐response curve of the area under the SR‐time curve versus log10 of the stimulus frequency before (vehicle control) and following 60 min of 20 mM capsazepine perfusion. The AUC data were normalized to the peak SR response during the control trial. The plateau of the area under the SR‐time curve was higher during control (101 ± 12 % max) than during capsazepine treatment (73 ± 18 % max, p =0.0045) while the EC50 was similar for both trials averaging 10.8 ± 2.1 Hz. The marked reduction in the plateau local sweat rate response supports the hypothesis that the TRPV1 receptor cation channel contributes to Ca++ influx during cholinergic‐mediated sweating.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Neurons in the Ventral Lateral Preoptic (vLPO) Area Inhibit Brown Adipose Tissue (BAT) Thermogenesis
Authors: Conceição Ellen P. , Madden Christopher J. , Morrison Shaun F.
Published: June 2021

Neurons in the preoptic area of the hypothalamus play important roles in thermoregulation. However, the subregions of the preoptic hypothalamus are heterogeneous, such that neuronal activation at some sites elicits hyperthermia, while others evoke hypothermia. Here we show that in urethane/chloralose‐anesthetized, artificially‐ventilated rats, neurons in the vLPO (0.0 to −1.44 mm caudal to bregma, 0.8 to 1.5 mm lateral to the midline, and −8.0 to 9.8 mm below the dura surface, incisor bar in flat skull position) have a hypothermic effect mediated by inhibition of sympathetic nerve activity (SNA) and BAT thermogenesis. The activation of cvLPO neurons with nanoinjections of NMDA (0.2 mM, 60 nl) evoked a complete inhibition of cold‐evoked BAT thermogenesis: BAT SNA (−97 %, p = 0.01), BAT temperature (TBAT, −0.4 °C, p = 0.01), expired CO2, (Exp CO2, −0.4 %, p = 0.0004), mean arterial pressure (MAP, −9 mmHg, p = 0.01) and heart rate (HR, −53 bpm, p = 0.0005). Similar BAT sympathoinhibitory responses were obtained with nanoinjections of bicuculline (BIC, 1.0 mM, 60 nl) in the vLPO. Under thermoneutral conditions, the inhibition of cvLPO neurons by activation of local GABAA receptors (muscimol, 1.2 mM, 60 nl) increased BAT SNA (+99 % p = 0.0001), TBAT (+2.2 °C, p = 0.0001), Exp CO2 (+1.0 %, p = 0.00003), and HR (+58 bpm, p = 0.007), with no change in MAP (p = 0.5). Nanoinjections of muscimol, or the glutamate receptor antagonists, AP5/CNQX, in the dorsomedial hypothalamus (DMH), or in the rostral raphe pallidus (rRPa), reversed the activation of BAT thermogenesis evoked by inhibition of vLPO neurons. Activation of neurons in vLPO inhibited the BAT thermogenesis evoked by BIC nanoinjections in the DMH, but not the increase in BAT SNA evoked by BIC nanoinjections in the rRPa. We conclude that vLPO contains BAT sympathoinhibitory neurons that mediate the warm ambient‐evoked inhibition of BAT thermogenesis through a direct or indirect GABAergic input to rRPa. Similarly to the cold‐evoked activation of BAT thermogenesis, that following inhibition of vLPO neurons requires the glutamatergic, BAT sympathoexcitatory pathway from DMH to BAT sympathetic premotor neurons in rRPa. These novel findings a key population of BAT sympathoinhibitory neurons in the central pathway mediating the skin warming‐evoked inhibition of BAT thermogenesis, requiring the addition of a BAT sympathoinhibitory pathway between vLPO and rRPa to the current model of central autonomic thermoregulation.

Support or Funding Information

This work was supported by NIH R01‐NS091066 (S.F.M.).

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Ventral Lateral Preoptic (vLPO) Neurons Inhibit Brown Adipose Tissue Thermogenesis during Warming of the Preoptic Area
Authors: Mohammed Mazher , Madden Christopher J. , Morrison Shaun F.
Published: June 2021

Brown adipose tissue (BAT) and shivering thermogenesis and cutaneous vasoconstriction are inhibited in warm climatic conditions to reduce heat production and increase heat dissipation, thereby maintaining core body temperature homeostasis. We tested the hypothesis that the hypothalamic preoptic area (POA) contains warm sensitive neurons (WSNs) that are activated by local warming to produce inhibition of BAT activity. In urethane/α‐chloralose‐anesthetized, artificially‐ventilated rats, warming the POA bilaterally with a thermode (two silver rods connected to a peltier device) increased POA temperature from 35 to 40°C and promptly inhibited skin cooling (35–36°C)‐evoked BAT sympathetic nerve activity (SNA) (from 1061±2.7 to 102±0.1 that corresponds to 100% reduction, p<0.001) and reduced BAT temperature (1.7±0.2, p<0.001), core temperature (0.3±0.1, p<0.05), expired CO2 (0.7±0.1%, p<0.001), heart rate (61±10, p<0.001) and mean arterial pressure (14±6, p<0.05). Bilateral nanoinjections of the GABAA‐agonist, muscimol (500 mM, 100 nl), into the ventral lateral preoptic area (vLPO) prevented (p<0.001) the local POA warming‐induced inhibition of BAT SNA and the reductions in BAT and core temperatures. Blockade of ionotropic glutamate receptors in vLPO with nanoinjections of AP5/CNQX also prevented (p<0.001) the local POA warming‐induced inhibitions of BAT thermogenesis. POA warming failed (p>0.05) to inhibit the elevated BAT SNA following blockade of local GABAA receptors with nanoinjections of bicuculline (BIC) in the rostral raphe pallidus (rRPa), but still effectively inhibited the elevated BAT SNA following BIC nanoinjections in the dorsomedial hypothalamus (DMH). Our results demonstrate that the POA warming‐evoked inhibition of BAT thermogenesis requires activation of GABAA receptors in rRPa, but not those in DMH. In addition, the finding that glutamate receptor blockade in vLPO prevents the POA warming‐induced inhibition of BAT activity, is consistent with WSNs glutamatergically exciting BAT sympathoinhibitory neurons in vLPO to produce the POA warming‐induced inhibition of BAT thermogenesis. These novel findings elucidate the central pathway mediating POA warming‐evoked inhibition of BAT thermogenesis and require the addition of a BAT sympathoinhibitory pathway between vLPO and rRPa to the current model of central autonomic thermoregulation.

Support or Funding Information

Supported by NIH R01091066 (SFM).

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sympathetic Nerve Fibers within the Cervical Vagus Nerve Do Not Innervate the Heart
Authors: Migirov Allan , Siano John , Dedkov Eduard I. , Zhang Youhua
Published: June 2021

Introduction

Chronic cervical vagus nerve stimulation has been introduced as a novel therapy for various diseases, including refractory epilepsy and chronic heart failure. Although it has been shown that the cervical vagus nerve contains sympathetic fibers, whether or not these sympathetic fibers innervate the heart is a subject of debate.

Methods

DiI, a plasma membrane lipophilic fluorescent dye (neuronal tracer) was applied on the epicardial surface of the heart at the right atrium‐right pulmonary vein junction and at the inferior vena cava and left atrium junction (these locations are known to have epicardial ganglia) in 4 rats to trace the nerve fibers innervating the heart. Two rats without DiI application served as controls. Right cervical vagus nerves were harvested 1 week after DiI application or sham surgery and processed for frozen histological sections. All sympathetic fibers in the cervical vagus nerve were visualized by immunostaining with anti‐tyrosine hydroxylase antibody, whereas those nerve fibers innervating the heart were expected to carry a fluorescent DiI dye.

Results

As shown in the figure, there were a few fibers stained with DiI (red color) in the cervical vagus nerve, which were not detected in controls. Sympathetic fibers in the vagus nerve (green color) were present in all animals. However, there was no overlap of the sympathetic fibers and DiI labeled nerve fibers in the vagus nerve.

Conclusions

Cervical vagus nerve contains sympathetic nerve fibers, however, these fibers do not innervate the heart.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Greater Beat‐To‐Beat Resting Blood Pressure Variability in Young Healthy African American Men
Authors: Young Benjamin E. , Vranish Jennifer R. , Peper Sara E. , Wang Jing , Keller David M. , Fadel Paul J.
Published: June 2021

It is well documented that African Americans (AA) are at a greater risk for the development of hypertension than Caucasian Americans (CA). Our laboratory has recently demonstrated exaggerated transduction of sympathetic nerve activity to blood pressure (BP) in young, healthy AA men compared to CA men. The influence of this greater sympathetic vascular transduction on BP variability is unclear. Although previous studies have reported greater BP variability in AA than CA based on 24‐hr ambulatory BP measurements, to date, no studies have investigated resting BP variability on a beat‐to‐beat basis in AA. Thus, we tested the hypothesis that young AA men would exhibit greater beat‐to‐beat BP variability in comparison to CA men. Heart rate (ECG), and beat‐to‐beat arterial BP (finger photoplethysmography) were continuously measured during a 20‐minute resting period in young, healthy CA (n=15) and AA (n=14) men. The arterial BP waveform was analyzed via Modelflow to estimate stroke volume, and used to calculate cardiac output (CO) and total peripheral resistance [TPR: mean arterial pressure (MAP) divided by CO]. Variance, range, and interquartile range were calculated for MAP, CO and TPR. Data are presented as mean ± standard error (SE). Despite similar average absolute resting systolic BP, diastolic BP, and MAP, compared to CA, AA exhibited larger MAP variance (CA: 19.2±2.6 mmHg2, AA: 32.3±4.0 mmHg2, p=0.009). In addition, the range (CA: 26.9±2.0 mmHg; AA: 33.2±1.8 mmHg, p=0.03) and interquartile range (CA: 5.7±0.4 mmHg; AA: 7.6±0.5 mmHg, p=0.007) of MAP were greater in AA than CA. Similar results were found for both systolic BP and diastolic BP. Interestingly, the variance of CO was not significantly different between groups (P=0.63), whereas the variance of TPR was significantly greater in AA than CA (P=0.03). Likewise, the TPR (but not CO) range, and interquartile range were greater in AA than CA. These findings demonstrate that, relative to CA, AA exhibit greater beat‐to‐beat BP variability which appears to be related to greater variability in TPR. Overall, these greater fluctuations in resting BP may constitute a source of future cardiovascular risk in AA men, and predispose them to the development of hypertension.

Support or Funding Information

Supported by NIH R15 HL130906.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.