bluuebunny/crossref_metadata_2025_split huggingface dataset:
CaMKII δ Deletion Protects Against Apoptosis In Myocardial Ischemia/Reperfusion Injury In Vivo
Authors: Ling Haiyun , Zhang Tong , Brown Joan Heller 
Published: June 2021

Background: The δ subunit of Ca2+/Calmodulin‐dependent protein kinase II (CaMKII) predominates in the heart. There is controversy regarding the role of CaMKII in myocardial ischemia/reperfusion, based largely on in vitro experiments using a pharmacological CaMKII inhibitor (KN‐93). The best evidence for in vivo function of CaMKII would come from the use of mice in which the gene is deleted. A mouse with CaMKII δ deletion has been recently developed in our lab. Methods and Results: CaMKII δ knockout mice and littermate controls were subjected to 1 h myocardial ischemia followed by 6 h reperfusion. Infarct size was measured by Evans blue/TTC staining. Apoptosis was assayed by DNA laddering. The expression of apoptosis related proteins (caspase‐3 and Bax) was also examed by Western blotting. Compared to WT controls, mice in which CaMKII δ was deleted showed a significant reduction in infarct size and DNA laddering, accompanied by attenuated Bax and caspase‐3 in the ischemic myocardium. Conclusion: CaMKII δ deletion protects against apoptosis in myocardial ischemia/reperfusion injury in vivo.This work was supported by HL80101.
Expression of Smac/DIABLO and Caspase‐3 Proteins in Rat Myocardium Suffered from Hypothermic Preservation
Authors: Zheng Ming‐zhi , Jiang Jian‐ping , Chen Ying‐ying , Shen Yue‐liang , Zheng Liang‐rong 
Published: June 2021

Objective: To investigate the effect of different duration of hypothermic preservation on the expression of Smac/DIABLO and caspase‐3 proteins in rat hearts.Methods: The Langendorff model of isolated rat heart was used. The hearts were stored in 4°C Celsior solution for different time (0, 3, 6, 9 or 12 h) followed by 60 min of reperfusion. The recovery of rate‐pressure product (RPP) in heart mitochondrial was measured at the end of reperfusion. Apoptotic cardiomyocytes were detected by TUNEL technique. The expression of Smac/DIABLO and Caspase‐3 proteins was also analyzed by Western blotting.Results: Prolonged the hypothermic preservation, the recovery of RPP decreased and the percentage of apoptotic cells enhanced in rat hearts. Long‐term preservation time‐dependently increased Smac/DIABLO and caspase‐3 proteins expression, the peak protein levels appeared at 9 h after preservation. Then levels of two proteins fell after 12 h of preservation.Conclusion: The results shown that prolonged the hypothermic preservation might lead to the expression of Smac/DIABLO protein and induce cardiomyocytes apoptosis, which may in turn result in malfunction of cardiomyocytes.This work was supported by the Science Foundation of Zhejiang Medical College (No.2006XZ04) and the National Natural Science Foundation of China (No.30470635).
BBB Na/H exchange: plasma membrane distribution of NHE1 and NHE2 isoforms and stimulation by arginine vasopressin
Authors: Lam Tina I. , O’Donnell Martha E. 
Published: June 2021

Cerebral edema formation in ischemic stroke involves increased activity of blood‐brain barrier (BBB) Na transporters through mechanisms not well understood. Na/H exchange inhibitors can reduce brain edema in rat models of ischemic stroke. We have found previously that cerebral microvascular endothelial cells (CMEC) express both NHE1 and NHE2 isoforms of the Na/H exchanger and that CMEC exchanger activity is stimulated by the ischemic factors hypoxia, aglycemia and arginine vasopressin (AVP). In the present study we evaluated BBB in situ for the presence of NHE isoforms and further, investigated the mechanism by which AVP stimulates the BBB Na/H exchanger. Western blot analysis and immunoelectron microscopy were used to evaluate NHE isoforms in freshly isolated rat cerebral microvessels and perfusion‐fixed rat brain, respectively. In addition, Na/H exchange activity of CMEC was evaluated by microspectrofluorometry, using the pH‐sensitive dye BCECF. NHE1 and NHE2 isoforms were found in the microvessels and in BBB in situ, with both isoforms predominantly in the luminal BBB membrane (70% for NHE1, 75% for NHE2). CMEC Na/H exchange activity was increased 2.3‐fold by AVP and 2.5‐fold by the V1 agonist Orn VP (both 100 nM, 5 min) but not by a V2 agonist (DDAVP). Our findings suggest that AVP stimulates luminal BBB NHE1 and/or NHE2 activity via a V1 AVP receptor pathway.Supported by NINDS and AHA Western States Affiliate
Acute exercise alters circulating and local tissue renin‐angiotensin systems
Authors: Chung Justin C.S. , Rush James W.E. 
Published: June 2021

Although the renin‐angiotensin system (RAS) plays an intricate role in coordinating vascular adaptations to exercise, there is a paucity of information regarding changes to circulating and local RAS associated with acute exercise. Thus, we investigated the modifications to circulating, aorta and kidney RAS in exercised male Sprague Dawley rats. Rats were exercised for 1h and euthanized immediately (IPEx) or 24h post exercise (24PEx, n=10 per group). Compared to non exercised control (CON), plasma ACE activity decreased IPEx, while 24PEx activity decreased further (85.61 ± 3.53 U/L; 75.28 ± 2.87 U/L; 62.03 ± 3.33 U/L, p<0.05 (U = μmol/min)). Plasma angiotensin II levels were increased IPEx (77.04 ± 16.71 pg/mL vs. 151.22 ± 25.42 pg/mL, p<0.05), but 24PEx levels were comparable to CON (81.19 ± 13.62 pg/mL, p>0.05). Compared to CON, aorta ACE activity decreased IPEx and remained blunted 24PEx (0.798 ± 0.03 U/g; 0.661 ± 0.05 U/g; 0.572 ± 0.03 U/g, p<0.05). Aorta ACE protein decreased ∼42% IPEx compared to CON and 24PEx (p<0.05). Kidney ACE activity increased IPEx (CON: 0.526 ± 0.03 U/g; IPEx: 0.648 ± 0.04 U/g; 24PEx: 0.489 ± 0.03 U/g, p<0.05). Upregulation of kidney ACE protein was observed IPEx (+42%) and 24PEx (+77%) (p<0.05). This study highlights changes in systemic and organ‐specific local RAS in response to acute exercise, which may be essential to the beneficial changes observed in chronic exercise.Funding: NSERC / HSFO
Acute volume expansion preserves orthostatic tolerance during whole‐body heat stress
Authors: Keller David M , Low David A. , Wingo Jonathan E. , Brothers R. Matthew , Davis Scott L. , Crandall Craig G. 
Published: June 2021

Whole‐body heat stress reduces orthostatic tolerance. The mechanisms responsible remain incompletely understood. The purpose of this study was to test the hypothesis that acute volume expansion improves orthostatic tolerance during passive heat stress (Δ core temperature ∼1.5 °C). Seven subjects participated in the following experimental protocol. Orthostatic tolerance was determined on 3 successive days using graded lower‐body negative pressure during normothermia (NT), whole‐body heating (WBH) and whole‐body heating with infusion of a volume expander (Dextran; WBH‐DEX) to restore central venous pressure (measured via a central venous catheter) to pre‐heat stress values. NT and WBH were randomized between Days 1 and 2, while WBH‐DEX was always performed on Day 3. As expected, orthostatic tolerance, expressed as cumulative stress index (CSI, mm Hg • min), was markedly reduced during WBH (182 ± 57 CSI) compared to NT (938 ± 152 CSI, P < 0.0001). Interestingly, WBH‐DEX (1109 ± 152 CSI) not only improved orthostatic tolerance relative to WBH (P < 0.0001), it also preserved tolerance compared to NT (P = 0.47). Therefore, despite marked reductions in orthostatic tolerance due to heat stress alone, acute volume expansion restored orthostatic tolerance similar to that observed during normothermic conditions.Supported by NIH Grant NIH‐HL61388 & HL84072
Gestational administration of glucocorticoid alters baroreceptor and chemoreceptor reflexes in rat
Authors: Polson Jaimie William , Paton Julian FR , Wolf Andrew R 
Published: June 2021

In the rat, administration of high levels of glucocorticoid during pregnancy produces late onset hypertension in the offspring. The causes of hypertension are not known, but may involve alterations in cardiovascular autonomic control. We examined baro‐ and chemoreflex changes in heart rate (HR) and sympathetic nerve activity (SNA) in the rat following gestational dexamethasone administration (DEX), using the in situ working heart brainstem preparation.Pregnant dams were administered DEX (200 μg/kg s.c.) at E15–16. At 3–5 weeks, perfusion pressure, HR, and activity of the phrenic nerve and thoracic sympathetic chain were measured in the in situ preparation of DEX offspring and naive controls. HR and SNA responses to baroreceptor (increase in pressure of 20–30 mmHg) and chemoreceptor (injection of 20–100 μL 0.03% NaCN) stimulation were measured. Baroreflex changes in HR gain (control, 1.3+0.2 v 0.8+0.2 bpm/mmHg) and SNA (16+4 v 6+1 %baseline/mmHg) were lower in the DEX rat than control (P<0.05, n=4), whereas the chemoreflex responses were augmented (bradycardia of 161+30 v 217+15 bpm and sympathoexcitation of 60+14 v 106+13 %baseline, P<0.05, n=4). The results indicate that cardiovascular autonomic reflexes are altered in the DEX hypertension in such a way as to facilitate an increase in sympathetic drive. This may contribute to the ontogeny of hypertension in this model.Support: British Heart Foundation
A2 noradrenergic neurons inhibit osmoreceptor‐induced pressor responses.
Authors: Freiria‐Oliveira Andre Henrique , Blanch Graziela Torres , Pedrino Gustavo R. , Cravo Sergio L. , Colombari Eduardo , Menani Jose Vanderlei , Colombari Debora S. A. 
Published: June 2021

A previous study showed that intragastric (ig) 2 M NaCl load increases mean arterial pressure (MAP) in rats with chronic electrolytic lesions of the commissural nucleus of the solitary tract (commNTS), but not in sham rats, suggesting that commNTS mechanisms inhibit pressor responses to osmoreceptor activation. In the present study we investigated the effects of ig 2 M NaCl load on MAP and heart rate (HR) in rats with lesions of the A2 noradrenergic neurons located in the NTS. Male Wistar rats (280–320 g) were submitted to lesions of DβH‐containing neurons in the commNTS achieved by injections of anti‐DβH‐saporin (12.6 ng/60 nl, n=11). Sham rats received injections of immunoglobulin‐G‐saporin (12.6 ng/60 nl, n = 5). Thirty days after saporin injections, MAP and HR were recorded for 60 min before and 60 min after ig 2 M NaCl load (2 ml). Intragastric 2 M NaCl increased MAP in A2 lesioned rats (14 ± 2 mmHg), but not in sham rats (3 ± 2 mmHg), without changing HR in both groups. A2 lesions produced no change on baseline MAP (112 ± 2 vs. sham: 118 ± 4 mmHg) and HR (341 ± 12 vs. sham: 382 ± 26 bpm) and also on baro and chemoreflex tested previously to ig 2 M NaCl. The results show that lesions of A2 noradrenergic neurons in the NTS facilitate pressor responses produced by increases in plasma osmolality, suggesting that A2 neurons are part of the mechanisms that inhibits osmoreceptor‐induced pressor responses.Supported by CNPq, FAPESP.
Kinins do not alter cardiovascular and sympathetic responses to isometric exercise in humans
Authors: Kuipers Nathan T , Sauder Charity L , Kearney Matthew L , Ray Chester A 
Published: June 2021

Bradykinin activates muscle afferents responsible for mediating the exercise pressor reflex in animals. This study was designed to test if cardiovascular and muscle sympathetic nerve activity (MSNA) responses to exercise are affected by kinins in humans. This study was conducted in a double‐blinded, placebo controlled, randomized manner. During drug treatment eight male (25±2 yr) subjects were given 20 mg of the ACE‐inhibitor quinapril to increase plasma kinins. Measurements included mean arterial blood pressure (MAP), heart rate, renal blood flow velocity (Doppler ultrasound), calf blood flow (plethysmography) and MSNA (microneurography). ACE‐inhibitor treatment lowered MAP (−9±3 mmHg) at baseline but did not alter heart rate, arterial blood pressure, renal and calf vascular conductance, and MSNA responses to ischemic isometric handgrip performed to fatigue. Cardiovascular and MSNA responses to postexercise muscle ischemia did not differ between treatments. This finding indicates that acute increases in kinins do not alter the exercise pressor reflex in humans.Research supported by NIH DC006459, HL077670, & MO1RR10732
Is it inflation or central inspiration that attenuates baroreflex sensitivity (BRS) in Man?.
Authors: Parkes Michael J. , Hollow Michael R. , Clutton‐Brock Thomas H 
Published: June 2021

Breathing reduces the heart period component of BRS. Is the cause predominantly pulmonary inflation or central inspiration? Hypocapnia (HA) augments the pulmonary stretch reflex but reduces the central respiratory rhythm. If HA further reduces BRS, the predominant cause of this respiratory attenuation is inflation, whereas if HA increases BRS the predominant cause is central inspiration.BRS was measured by spontaneous sequence analysis in 7 healthy subjects in eupnea (PetCO2 38 ± 1 mmHg) and during mechanical hyperventilation by facemask, where subjects breathed with the ventilator, in either normocapnia or HA.In eupnea BRS was attenuated in inflation/inspiration vs. deflation/expiration (11 ±3 ms/mmHg vs. 24 ±7 ms/mmHg, P<0.005). Averaged mean blood pressure was 90 ±3 mmHg and mean heart period was 0.88 ± 0.06 s. Mechanical hyperventilation (PetCO2 = 39 ±1 mmHg) had no signficant effects vs. eupnea on blood pressure, heart period or BRS.HA (PetCO2 = 23±0 mmHg) had no significant effect on blood pressure or heart period but reduced mean BRS in inflation/inspiration to 6±1 ms/mmHg (n=6, P< 0.001). This effect also carried over to reduce BRS (7 ± 2 ms/mmHg, n=7, P<0.05) in deflation/expiration.Because HA further reduces (rather than increases) BRS, we conclude that under these conditions the cause of the respiratory attenuation of BRS is predominantly inflation rather than central inspiration.
A novel effect of P2X7 receptor antagonist ‐ oxidized ATP in mouse aorta
Authors: Chiao Chin‐Wei , Tostes Rita C. A. , Webb R. Clinton 
Published: June 2021

Introduction: The P2X7 receptor is an unusual non‐desensitizing, cation selective, ion channel directly gated by extracellular ATP or ATP analogs. It is involved in several processes relevant to inflammation and immunity. Oxidized ATP (oATP) is a potent irreversible antagonist of P2X7 receptor, and it is not influenced by the presence of extracellular Na+ or K+. In our previous vascular functional study, we found that high concentration of oATP inhibits contractile response to PE.Hypothesis: oATP induces a factor to abolish the contractile response of PE in mouse aortic rings.Methods & Results: Vascular reactivity was evaluated using standard methods in aortic rings, with endothelium, from male C57Bl/6 mice. Incubation with oATP (24 h) inhibited 10−6M PE‐induced contractions in a concentration‐dependent way: oATP 50 μM (80.37±3.37 %, normalized to 120 mM KCl), 100 μM (47.11±1.54 %), 150 μM (46.43±4.64 %), and 250 μM (32.77±4.37 %). L‐NAME or 1400W reversed the abolished PE contractile response in 250 μM oATP. However, indomethacin did not. oATP did not alter eNOS, iNOS, or nNOS protein expression, but decreased COX2 protein expression.Conclusion: oATP abolished PE‐induced contractile response in mouse aortic rings. This effect might be induced by activation of the nitric oxide signaling pathway.
Functional consequences of overexpression of ETA in adult rat ventricular myocytes
Authors: Chung Ka Young , Walker Jeffery W 
Published: June 2021

Activation of ETA, the predominant ET‐1 receptor subtype in myocardium, is known to induce a positive inotropic effect (PIE). In heart failure, ETA is often upregulated presumably as a compensatory measure. In this study, we explored functional consequences of upregulation of ETA in adult rat ventricular myocytes (ARVM). To investigate physiological function, we examined three twitch parameters (PIE, diastolic shortening and twitch broadening) and measured [Ca2+]i in control and ETA overexpressed ARVM. In control ARVM, ET‐1 induced ~30% PIE and ~1% diastolic shortening, but twitches were not broadened. Overexpression of ETA significantly increased PIE to ~60%, diastolic shortening to ~7% and twitch broadening by ~15%. Peak [Ca2+]i and basal [Ca2+]i correlated with PIE and diastolic shortening respectively, but the slopes were larger in ETA overexpressed ARVM. Therefore, changes in [Ca2+]i induced significantly more twitch responses in ETA overexpressed ARVM. These results suggest that ETA‐overexpression has a substantial impact on the twitch properties including i) prolongation of twitch duration, and ii) an increase in diastolic cell shortening. Such ET‐1 effects mediated through upregulated ETA may contribute to diastolic dysfunction (delayed relaxation and elevated ventricular end diastolic pressure) in heart failure.This study is supported by an AHA Predoctoral fellowship and NHLBI.
Abnormalities in the catabolic fate of long‐chain fatty acids and glucose in compensated murine cardiac hypertrophy
Authors: Wambolt Richard B , Parsons Hannah L , Bohunek Lubos , Allard Michael F 
Published: June 2021

Reduced oxidative catabolism of fatty acids (FAO) and accelerated rates of non‐oxidative glucose catabolism (NOG) are recognized metabolic abnormalities in genetic and acquired models of cardiac hypertrophy (H) in rats, but are less well characterized in mice. We determined catabolic fates of long‐chain fatty acid (palmitate – P) and glucose (G) in compensated non‐hypertrophied (C) and hypertrophied (H) hearts from sham‐operated and abdominal aortic‐constricted CD1 mice. Hearts were perfused with either 1.2mM P, 5.5mM G, 0.5mM lactate and 20mU/L insulin (Series 1) or 0.6mM P, 5.5mM G, 1.5mM lactate, 0.5mM pyruvate and 20mU/L insulin (Series 2 ‐ reflects in vivo substrate concentrations in mice). No differences in heart function, expressed as cardiac power (ml·mmHg·min−1), were observed between C and H in either Series 1 (10.9 ± 0.6 vs. 10.4 ± 0.3) or Series 2 (12.8 ± 0.4 vs. 13.1 ± 0.6).Results:Substrate catabolism in a murine model of acquired compensated H resembles that in models of H in rats. Abnormalities in NOG persist in hearts exposed to a physiologically relevant substrate mixture, even though significant differences in FAO disappear, suggesting that defects in NOG are a key metabolic abnormality occurring early in the development of H.
Markers of Mitochondrial Biogenesis following 3 days of Cycling
Authors: Dumke Charles L , Nieman David C , Davis J Mark , Murphy E. Angela , Carmichael Martin D , Henson Dru A , Quindry John C , Utter Alan C , Triplett N. Travis , McAnulty Steven R , McAnulty Lisa S 
Published: June 2021

Exercise increases mRNA for several genes involved in mitochondrial biogenesis. Less is known about how these genes respond to several successive days of intensive exercise.PURPOSE:To examine the effects of 3 h of intensive cycling over 3 successive days on gene expression in humans.METHODS:Twenty trained cyclists were tested for VO2max (54.7±1.1 ml.kg‐1.min‐1). The subjects cycled at 57% wattsmax for 3 h using their own bicycles on CompuTrainer™ Pro Model trainers (RacerMate, Seattle, WA) on 3 successive days. Muscle biopsies were obtained from the vastus lateralis pre‐ and post‐exercise on days 1 and 3. Muscle samples were analyzed (2(time) X 2(day) repeated measures ANOVA) for gene expression of cytochrome C, peroxisome proliferator receptor gamma coactivator‐1 alpha (PGC‐1A), citrate synthase, and Sirt‐1.RESULTS:Of the genes analyzed the following showed significant increases pre‐post 3 h rides: cytochrome C (P=0.03), PGC‐1A (P<0.001), and Sirt‐1 (P=0.05). The following genes showed significant effects from days 1 to 3: cytochrome C (P<0.001) and citrate synthase (P=0.009).CONCLUSION:Three successive days of intensive cycling resulted in upregulation of mRNA for mitochondrial enzymes and biogenesis markers in these trained subjects. These data contribute to the understanding of mitochondrial enzyme expression during prolonged exercise training.
Effects of post exercise supplementation with protein and carbohydrate on lean tissue mass gains during 70 days of resistance training in healthy males and its association with mediators of the molecular regulation of muscle mass
Authors: Greenhaff Paul Leonard , Karagounis Leonidas G. , Pittas George , Layfield Robert 
Published: June 2021

We studied the effect of 70 days of resistance training (RT), or RT plus protein and carbohydrate ingestion, on lean tissue and fat mass gains and mediators of anabolic signalling and MAFbx protein expression in human muscle. Untrained subjects performed supervised RT (3 times/week) for 70 days at 80% of 1 rep. max. (reevaluated every 2 weeks and adjusted accordingly). Immediately after each training session, subjects consumed 3g of flavourings (Control, n=8) or 50g whey protein and 50g dextrose (ProDex, n=8) in a non‐isocaloric solution. Body composition (DEXA) and a quadriceps biopsy sample were obtained at baseline and day (d)2, d35 and d70 (all 24h following training). Lean tissue mass increased from baseline by d35 and d70 in Control (P<0.01, P<0.001, respectively) and ProDex (P<0.001, P<0.001, respectively), but there was no difference between groups. Similarly, fat mass declined in both groups with training, with no difference between groups. Compared to Control, ProDex was associated with increased phosphorylation of Akt/PKB (d2, P<0.01; d70, (P<0.05), mTOR (d70, P<0.05), p70S6k (d70, P<0.001) and decreased expression of MAFbx (d2, P<0.01) protein. Post‐exercise ingestion of ProDex over 70 days RT had no additional effect on body composition than training alone, despite differences in mediators of the molecular regulation of muscle mass.This study was funded by Iovate Inc.
Twenty weeks of whole body resistance training improves the response of leg blood flow to feeding at rest and after exercise
Authors: Phillips Bethan , Wilkes Emilie , Smith Kenneth , Baker Margaret , Rennie Michael 
Published: June 2021

There is little information on how resistance training affects muscle blood flow responses at rest to a meal and to prior exercise. Therefore, we studied the response to feeding with or without acute resistance exercise (RE) before and after 20 w of whole body RE training (thrice weekly, 70% 1RM, with 1RM re‐assessments monthly). Before and after training, 10 subjects, 8 male and 2 female (21–73 y), (BMI >18<28) performed 6×8 isotonic unilateral leg extensions at 75% 1RM before intermittent feeding (at 4.25×BMR for 2.5 h). Femoral artery blood flow was measured by Doppler ultrasound at rest in both legs throughout.Before training, feeding alone or exercise with feeding increased resting blood flow. After training, blood flows in all conditions were increased. Whole body resistance training increases the responses of resting leg blood flow to feeding alone or feeding after exercise. Such an adaptation is likely to increase nutrient delivery to leg muscle and help maintain muscle mass, as well as potentially increasing insulin sensitivity.Supported by UK BBSRC ((BB/XX510697/1 and BB/C516779/1) and a European Union EXEGENESIS program grant.