Many studies documented the relationship between elevated plasma concentrations of natriuretic peptides and cardiovascular diseases, especially heart failure. However, it is still uncertain whether physical exercise leads to a significant release of natriuretic peptide in healthy subjects. The aim of this study was to determine the effect of maximal physical activity on plasma BNP concentrations in healthy individuals within 3 hours after the short-term exercise. BNP plasma concentrations were measured in 15 healthy volunteers before, immediately after as well as 1 hour and 3 hours after bicycle spiroergometry. Maximal workload and exercise capacity were assessed in watts, wattseconds, metabolic equivalents and VO2max. Mean BNP plasma levels before, immediately after, 1 hour and 3 hours postexercise were 19.4±2.5; 30.6±4.7; 17.9±2.5 and 18.7±3.1 pg/ml, respectively. The increase of BNP concentrations immediately after exercise was statistically significant (p=0.0017) compared to baseline values. We did not find any correlation between the post-exercise increase of BNP levels and age, body mass index, maximal workload or exercise capacity. In conclusion, short-term maximal physical exercise in healthy individuals led to a fast and transient rise of plasma BNP concentrations, which remained well within normal range and far below the cut-off value for heart failure (100 pg/ml)., J. Krupička ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Activation of sublobule IX-b of the cerebellar vermis evokes hypotension, bradycardia and decrease of the phrenic nerve activity in the anesthetized animal. Cardiac performance during the isovolumic phases of systole and relaxation can be evaluated by dP/dt max, Vpm, dP/dt/DP40 and τ, respectively. In the present study, we evaluated the changes on cardiac function evoked by the stimulation of sublobule IX-b. New Zealand white rabbits were anesthetized, paralyzed and artificially ventilated. A posterior craniotomy was made to reveal and stimulate the cerebellar uvula (4 s train; 50 Hz; 1 ms; 20 μA). The femoral artery and veins were cannulated and a Swan-Ganz catheter was advanced in the upper abdominal aorta to control afterload when inflating the balloon. The left ventricle was catheterized with a Millar catheter. Blood pressure, heart rate, left ventricular pressure were monitored. Results showed a significant decrease on sublobule IX-b stimulation of all the indices of systolic function and an increase of τ indicating a decrease in the speed of the relaxation. These data provide the first evidence of the influence of sublobule IX-b on cardiac function. They may contribute to the understanding of the origin the cardiovascular changes that were observed in two patients with vermian and paravermian hemorrhage., I. Rochas, V. Gonçalves, M. J. Bettencourt, L. Silva-Carvalho., and Obsahuje bibliografii a bibliografické odkazy
We evaluated the effects of exercise on the vascular constrictor responses to α-adrenergic stimulation in the db/db mice. Twenty male db/db and their age-matched wild-type (WT) mice were exercised (1 hour/day, five days a week). Mice were anesthetized 7 weeks later, thoracic aortae were mounted in wire myograph and constrictor responses to phenylephrine (PE, 1 nM-10 μM) were obtained. Citrate synthase activity measured in the thigh adductor muscle was significantly increased in db/db mice that were exercise trained. Maximal force generated by PE was markedly greater in db/db aortae and exercise did not attenuate this augmented contractile response. Vessels were incubated with inhibitors of nitric oxide synthase (L-NAME, 200 μM), endothelin receptors (bosentan, 10 μM), protein kinase C (PKC) (calphostin C, 5 μM), cyclooxygenase (indomethacin, 10 μM) or Rho-kinase (Y-27632, 0.1 μM). Only calphostin-C normalized the augmented PE-induced constriction in db/db and db/db- exercised mice to that observed in WT (p<0.05). Cumulative additions of indolactam, a PKC activator, induced significantly greater constrictor responses in aortic rings of db/db mice compared to WT and exercise did not affect this response. Our data suggest that the augmented vasoconstriction observed in the aorta of db/db mice is likely due to increased PKC activity and that exercise do not ameliorate this increased PKC-mediated vasoconstriction., M. Khazaei, F. Moien-Afshari, T. J. Kieffer, I. Laher., and Obsahuje bibliografii a bibliiografické odkazy
Several diseases induce hypermetabolism, which is characterized by increases in rest ing energy expenditures (REE) and whole body protein loss. Exaggerated protein degradation is thought to be the driving force underlying this response. The effects of caspase and calpain inhibitors on REE in physiological and hypermetabolic conditions, how ever, are unknown. Thus, we studied whether MDL28170 (calpain inhibitor) or z-VAD-fmk (caspase inhibitor) affect REE under physiological conditions and during hypermetabolism post -burn. Rats were treated five times weekly and observed for 6 weeks. Treatmen t was started 2 h (early) or 48 h ( late) after burn. In normal rats, MDL28170 transiently increased REE to 130 % of normal during week 2-4. z-VAD-fmk reduced REE by 20-25 % throughout the observation period. Within 14 days after burns, REE increased to 13 0±5 % . Whereas MDL28170/ early treatment did not affect REE, MDL28170/ late transiently increased REE to 180±10 % of normal by week 4 post- burn. In contrast, with z -VAD -fmk/ early REE remained between 90-110 % of normal post- burn. z-VAD-fmk/ late did not affect burn-induced increases in REE. These data suggest that caspase cascades contribute to the development of hypermetabolism and that burn-induced hypermetabolism can be pharmacologically modulated. Our data point towards caspase cascades as po ssible therapeutic targets to attenuate hypermetabolism after burns, and possibly in other catabolic disease processes., P. G. Vana, H. M. LaPorte, R. H. Kennedy, R. L. Gamelli, M. Majetschak., and Obsahuje bibliografii
Atrial natriuretic peptide antifibrotic properties are mainly described in cardiac myocytes or in induced cardiac myofibroblasts (Angiotensin II or TGF-β induced differentiation). In the present work, we investigate the effects of ANP/NPRA/cGMP system in modulating rat cardiac fibroblasts function. Cardiac fibroblasts were isolated from adult Wistar male rats and cultured in the presence of serum in order to induce fibroblasts differentiation. Cultures were then treated with ANP (1 μM), 8-Br-cGMP (100 μM) or IBMX (100 μM), a non-specific phosphodiesterases inhibitor. ANP significantly decreased proliferation rate and collagen secretion. Its effect was mimicked by t he c GMP a nalog, w hile c ombining A NP w ith 8 -Br-cGMP did not lead to additional effects. Moreover intracellular cGMP levels were elevated when cells were incubated with ANP confirming that ANP intracellular pathway is mediated by cGMP. Additionally, immunoblotting and immunofluorescence were used to confirm the presence of guanylyl cyclase specific natriuretic peptide receptors A and B. Finally we scanned specific cGMP dependent PDEs via RT-qPCR, and noticed that inhibiting all PDEs led to an important decrease in proliferation rate. Effect of ANP became more prominent after 10 culture days, confirming the importance of ANP in fibroblasts to myofibroblasts differentiation. Uncovering cellular aspects of ANP/NPRA/cGMP signaling system provided more elements to help understand cardiac fibrotic process., M. Moubarak, C. Magaud, Y. Saliba, A. Chatelier, P. Bois, J.-F. Faivre, N. Farès., and Obsahuje bibliografii
Various types of mechanosensitive ion channels, including cationic stretch-activated channels (SAC NS ) and stretch-activated BKca (SAKca) channels, modulate heart rhythm. Bepridil has been used as an antiarrhythmic drug with multiple pharmacological effects; however, whether it is effective for mechanically induced arrhythmia has not been well investigated. To test the effects of Bepridil on SAKca channels activity, cultured chick embryo nic ventricular myocytes were used for single - channel recordings. Bepridil significantly reduced the open probability of the SAKca channel (PO). Next, to test the effects of bepridil on stretch-induced extrasystoles (SIE), we used an isolated 2-week-old Langendorff-perfused chick heart. The left ventricle (LV) volume was rapidly changed, and the probability of SIE was calculated in the presence and absence of bepridil, and the effect of the drug was compared with that of Gadolinium (Gd3+). Bepridil decreased the probability of SIE despite its suppressive effects on SAKca channel activity. The effects of Gd3+, which blocks both SAKca and SACNS , on the probability of SIE were the same as those of bepridil. Our results suggest that bepridil blocks not only SAKc a channels but possibly also blocks SACNS , and thus decreases the stretch -induced cation influx (stabilizing membrane potential) to compensate and override the effects of the decrease in outward SAKca current (destabilizing membrane potential)., H. Jin, G. Iribe, K. Naruse., and Obsahuje bibliografii
Beta-hydroxy-beta-methylbutyrate (HMB) is a leucine metabolite with protein anabolic effects. Since HMB is synthesized in the liver, unique effects of exogenous HMB intake may be hypothesized in subjects with liver disease, in which muscle wasting is frequently found. We studied effects of HMB on the liver and soleus (SOL) and extensor digitorum longus (EDL) muscles in partially-hepatectomized (PH) rats. HMB or saline was infused using osmotic pumps to PH or sham-operated rats for 7 days. We found lower body weight and protein content in EDL of PH rats treated with saline than in sham-operated animals. These effects were insignificant in HMB treated animals. In blood plasma of PH rats treated with HMB we found lower concentrations of creatinine and higher concentrations of urea and branched-chain amino acids (BCAA; valine, leucine, and isoleucine) than in PH animals treated with saline. HMB increased BCAA concentrations in SOL and EDL of PH animals and decreased proteolysis in EDL of both sham-operated and PH animals. In the livers of PH rats treated with HMB we found higher DNA content, DNA fragmentation, and BCAA concentrations than in saline-treated animals. The results indicate that HMB affects metabolism of BCAA and has positive influence on protein balance in muscles. Further studies are needed to clarify the effect of HMB on liver regeneration., M. Holeček, M. Vodeničarovová., and Obsahuje bibliografii
The effects of exercise on mechanical hyperalgesia, joint contracture, and muscle injury resulting from immobilization are not completely understood. This study aimed to investigate the effects of cyclic stretching on these parameters in a rat model of chronic post-cast pain (CPCP). Seventeen 8-week-old Wistar rats were randomly assigned to (1) control group, (2) immobilization (CPCP) group, or (3) immobilization and stretching exercise (CPCP+STR) group. In the CPCP and CPCP+STR groups, both hindlimbs of each rat were immobilized in full plantar flexion with a plaster cast for a 4-week period. In the CPCP+STR group, cyclic stretching exercise was performed 6 days/week for 2 weeks, beginning immediately after cast removal prior to reloading. Although mechanical hyperalgesia in the plantar skin and calf muscle, ankle joint contracture, and gastrocnemius muscle injury were observed in both immobilized groups, these changes were significantly less severe in the CPCP+STR group than in the CPCP group. These results clearly demonstrate the beneficial effect of cyclic stretching exercises on widespread mechanical hyperalgesia, joint contracture, and muscle injury in a rat model of CPCP., Kazuhiro Hayashi, Saori Fukuyasu-Matsuo, Takayuki Inoue, Mitsuhiro Fujiwara, Yuji Asai, Masahiro Iwata, Shigeyuki Suzuki., and Obsahuje bibliografii
Effects of ectopic pacing on left ventricular repolarization were studied in six anesthetized open-c hest chickens. In each animal, unipolar electrograms were acquired from as many as 98 sites with 14 plunge needles (seven transmural locations between epicardium and endocardium in each needle). Activation-recovery intervals (ARIs), corrected to the cycle length, were used for estimating repolarization. At baseline, the nonuniform ARI distribution in the left ventricle resulted in the apicobasal differences being greater than the transmural gradient. Nonuniform ARI prolongation caused by ectopic pacing resulted in decreasing the transmural repolarization gradient and increasing the differences in th e apex-to-base direction. The basal, but not apical transmural differences contributed to the total left ventricular transmural gradient. The total left ventricular apicobasal gradient was contribute d by the apicobasal differences in mid-myocardial and subendoc ardial layers more than in subepicardial ones. Thus, in in situ chicken hearts, the transmural and apicobasal ARI gradients exist within the left ventricle with the shortest ARIs in the basal subepicardium and the longest ARIs in the subendocardium of th e apical and middle parts of the left ventricle. Apicobasal compar ed to transmural heterogeneity of local repolarization properties contributes more to the total left ventricular repolarization gradient., S. N. Kharin, D. N. Shmakov, N. A. Antonova., and Obsahuje bibliografii
We previously found that Endothelin-11-31 (ET-11-31) exhibited a pro-arrhythmogenic effect in isolated rat hearts. In this study, we further investigated the effects of ET-11-31 on a cell viability and observed [Ca2+]i in cultured cardiomyocytes. Cultured neonatal rat cardiomyocytes were treated with 0.1, 1, and 10 nM ET-11-31 for 24h in the presence or absence of ETA receptor antagonist (BQ123) or phosphoramidon, a NEP/ECE inhibitor. Cell injury was evaluated by supernatant lactate dehydrogenase (LDH) assay, superoxide dismutase (SOD activity, and malondialdehyde (MDA) content. Cell viability was assessed by MTT assay. [Ca2+]i was measured with Fluo-3/AM under a laser confocal microscope. 1) ET-11-31 dose-dependently increased LDH release and decreased cell viability. 2) LDH and MDA levels were significantly elevated and SOD activity decreased after administration of 1 nM ET-11-31 for 24h, and these changes were markedly attenuated by 1 uM BQ123. 3) Exposure to 10 nM ET-11-31 caused a continuous increase in [Ca2+]i to cultured beating cardiomyocytes and termination of [Ca2+]i transient within 6 min, and this change was reversed by 1 uM BQ123 and attenuated by 0.5 mM phosphoramidon. These results suggest that ET-11-31 could cause cell injury, and that the effect of ET-11-31 on [Ca2+]i transients is mainly mediated by ETA receptor and partially attributed to the conversion of ET-11-31 to ET-11-21., A.-J. Ren, X. Yuan, L. Lin, Y.-X. Pan, Y.-W. Qing, W.-J. Yuan., and Obsahuje bibliografii a bibliografické odkazy