Role of the visceral nerve in heart rate variations during different behavioral patterns in Megalobulimus sanctipauli (mollusca,gastropoda, pulmonata)

• 1.1. The role of the visceral nerve in mediating the changes in heart rate associated with different behavioral patterns was investigated in Megalobulimus sanctipauli.
• 2.2. The results of acute and chronic denervation experiments indicate that the visceral nerve has no excitatory or inhibitory tonic action on the heart of snails retracted into the shell, nor does it account for the increase in heart rate associated with the locomotion and feeding behaviors.
• 3.3. These changes in heart rate are, probably, indirect effects of increased activity such as an increase in venous return.
• 4.4. The visceral nerve is responsible for approximately 3/4 of the increase in heart rate associated with the first minute of extrusion.
• 5.5. The small increase in heart rate observed in denervated animals is probably caused by an increase in venous return generated by muscle activity that forces the head and food out of the shell.

     

Akt signaling pathway in pacing-induced heart failure

Marked changes in energy substrate utilization occur during the progression of congestive heart failure (CHF) where fatty acid utilization, as the primary source of cardiac energy, is severely diminished, oxidative phosphorylation is down-regulated, and glucose uptake and utilization increase. Neither the signaling events or the molecular basis for the shift in substrate utilization have yet been elucidated. This study was designed to examine in the canine model of paced-induced CHF, the potential role of the Akt pathway in signaling the metabolic transitions central to progression to heart failure. Myocardial Akt levels were elevated in early heart failure (after 1–2 weeks of pacing) accompanied by increased levels of oxidative stress, cytokine tumor necrosis factor- (TNF-) and free fatty acid accumulation, reduced activity levels of mitochondrial respiratory complexes III and V and apoptosis initiation. At severe heart failure (3–4 weeks of pacing), there was significant further increase in myocardial apoptosis, with pronounced decline in myocardial Akt kinase activity. At this later stage, there were no further changes in free fatty acid accumulation, complex V activity or in oxidative stress levels indicating that these changes primarily occurred in the earlier stage of evolving heart failure. In contrast, during severe heart failure, both the reduction in complex III activity and increase in TNF- level became more pronounced. Our data provide critical support for the hypothesis that the Akt signaling pathway is a contributory element in the early signaling events leading to the progression of pacing-induced heart failure, accompanying the shift in substrate utilization. (Mol Cell Biochem 268: 103–110, 2005)     

Changes in autonomic control of heart associated with classical appetitive conditioning in rats.

The aim of this study was to examine the changes in autonomic control of the heart associated with classical appetitive conditioning in rats. We trained rats to learn that a movement into a test chamber was followed by delivery of reward (contextual conditioning) and performed power spectral analysis of heart rate variability from electrocardiograms recorded using the telemetry system. We investigated the sympathovagal balance of autonomic regulation of the heart in response to not only the conditioned stimulus (the movement into the test chamber), but also the unconditioned stimulus (reward), and compared the results of these two kinds of emotional states; it might be considered that "the reward-expecting state" is evoked by the conditioned stimulus and "the reward-receiving state" is evoked by the unconditioned stimulus in rats. The reward-expecting state resulted in a significant increase in both low frequency (LF) power and high frequency (HF) power with no change in heart rate (HR) and LF/HF ratio, indicating that both sympathetic and parasympathetic activity increased with no change in sympathovagal balance. The reward-receiving state resulted in a significant increase in HR and a significant decrease in LF power, HF power, and LF/HF ratio, indicating that both sympathetic and parasympathetic activity decreased with predominance in the parasympathetic activity. These results suggest that the method performed in our present study might be useful for distinguishing between two different emotional states evoked by classical appetitive conditioning in rats.     

Changes in energy metabolism in several brain regions and vegetative responses of white rats during neurotization

Changes of vegetative reactions and cytochrome oxidase (CChO) activity in various brain structures were studied in rats during neurotization. One week neurotization led to an increase of arterial blood pressure, respiration rate, cardiac stroke volume and heart rate. In three weeks of neurotization there was a decrease of stroke volume accompanied by an increase of heart rate and some decrease or respiration rate leading to a reduction of oxygen consumption. Neurotization during one and especially three weeks elicited an enhancement of CChO activity in various brain areas, more pronounced in the cerebral cortex. A four week "rest" after neurotization during three weeks normalized the CChO activity. CChO activation during neurotization is supposed to be one of the mechanisms of adaptation to hypoxia accompanying neurosis.     

Function of the membrane lipids of the heart sarcoplasmic network in izadrin myocarditis studied by using a pyrene probe

The fluorescent hydrophobic pyrene probe was employed to study the viscosity of membrane lipids of rat heart sarcoplasmic reticulum in isoproterenol myocarditis. During pyrene incorporation into the reticulum obtained from the affected myocardium, the increase in the microviscosity occurred at lower temperatures and more rapidly both in "bound" and "free" membrane lipids as compared with normal. The increase of the viscosity of the reticulum membranes in isoproterenol myocarditis was accompanied by a lowering of the activity of Ca, Mg-ATPase of the sarcoplasmic reticulum coupled with an elevation of the content of lipid peroxidation products.     

Alterations in norepinephrine,serotonin, c-AMP,and transsynaptic induction of tyrosine hydroxylase after spinal cord transection in the rat

Tyrosine hydroxylase (TH) activity and the concentrations of norepinephrine (NE), serotonin (5-HT), and cyclic adenosine 3, 5-monophosphate (c-AMP) were measured in the heart, adrenals, and brain stem of paraplegic rats. Following spinal cord transection NE concentration in the heart dropped to 30% within 24 hours and that of 5-HT decreased to 60% of control. Tyrosine hydroxylase activity and c-AMP levels in the brain stem were elevated while NE concentration remained low. At seven days, however, NE and 5-HT levels were higher than in controls while TH activity and c-AMP concentration dropped to control levels. The increase in TH activity in the brain stem may be due to curtailed end-product feedback inhibition and to reduced receptor activation. The sustained induction of the adrenal TH is probably a consequence of a continual stimulation of splanchnic nerves.     

Lizard heart rate and motor activity relationships in the circadian and ultradian ranges

• 1.1. The heart rate and motor activity of lizards (Gallotia galloti) maintained in a light-dark cycle (12:12 hr) and with changing cyclic temperature were recorded. Both variables showed a circadian pattern, motor activity variations leading heart rate by approximately 110 min.
• 2.2. Results from cross spectral analysis showed that heart rate was highly correlated with temperature and both variables were changing practically in phase. However, motor activity and temperature were less correlated and in this case motor activity led temperature by approximately 100 min.
• 3.3. In the ultradian range, two periodicities could be distinguished in the power spectra of motor activity and heart rate variations during the day: one between 0.019 and 3.9 × 10⁻³ cycles/min (central peak around 85 min period) and another, of lower power, between 0.05 and 0.02 cycles/min (central peak around 34 min period). During the night, only the heart rate showed both periodicities but with a lower amplitude.
• 4.4. The presence of ultradian oscillations in heart rate during the night suggested that they do not depend on motor activity which was almost absent during that daily period.
• 5.5. Motor activity and heart rate were also highly correlated in the ultradian range, motor activity leading heart rate by around 5 min at the 85 min main peak.

     

Concerning the decreased D-3-hydroxybutyrate dehydrogenase activity in the liver and heart of hyperthyroid rats

Summary Whereas in rat liver mitochondria the hyperthyroid state causes an increase both in fatty acid unsaturation and in the Ea of D-3-hydroxybutyrate dehydrogenase and a decrease in phase transition temperature, in hyperthyroid rat heart mitochondria these changes are negligible. D-3-hydroxybutyrate dehydrogenase in both the liver and the heart mitochondria of hyperthyroid rats is reduced by about 35% [l2] but this reduction is not due to changes in membrane fluidity in either tissue. Hypothyroidism, on the other hand, affects BDH activity in neither heart nor liver.Abbreviations BDH D-3-hydroxybutyrate dehydrogenase - PTU 6n-propyl-2-thiouracil - T₃,3,3 5-L-triiodothyronine - Tm temperature phase transition - Ea apparent activation energy     

Stimulation of ornithine decarboxylase activity in rat tissues by growth hormone and by serum growth factor from rats infested with spargana of Spirometra mansonoides

Ornithine decarboxylase activity was studied in heart, kidney, liver, thymus, lung, spleen, skeletal muscle and fat of hypophysectomized rats after growth hormone treatment. A marked increase in enzyme activity was observed in kidney and liver, and a significant increase in heart and thymus at 4 h after injection of growth hormone. The kidney was the most responsive organ with an increase in activity of about 100 fold. The enzyme activity in kidney responded to a dose of 10 μg of growth hormone. Daily injection for 12 days raised activity only in the heart. Infestation for 6–13 days with spargana of Spirometra mansonoides, which also causes growth of hypophysectomized rats, increased enzyme activity in the heart and thymus. Intravenous injection of serum of hypophysectomized rats infested with spargana of Spirometra mansonoides caused a significant increase in the enzyme activity in liver and kidney after 4 h. Growth hormone and the serum growth factor of sparganosis seem to share the characteristic of causing an early increase in ornithine decarboxylase activity in rat tissues. The marked response in kidney and liver raises the possibility that these organs are the primary targets of both substances.     

High-density lipoproteins protect endothelial cells from tumor necrosis factor-alpha-induced apoptosis

High-density lipoproteins (HDL) levels have been shown to be inversely correlated with coronary heart disease, but the mechanisms of the direct protective effect of HDL on endothelial cells are not fully understood. The apoptosis of endothelial cells induced by cytokines and/or oxidized low-density lipoproteins, etc. may provide a mechanistic clue to the "response-to-injury" hypothesis of atherogenesis. Here we report that HDL prevent the apoptosis of human umbilical venous endothelial cells (HUVECs) induced by tumor necrosis factor-alpha (TNF-alpha) via an inhibition of CPP32-like protease activity. The incubation of HUVECs with TNF-alpha significantly increased the CPP32-like protease activity, and induced apoptosis. Preincubation of HUVECs with HDL before incubation with TNF-alpha significantly suppressed the increase in the CPP32-like protease activity, preventing apoptosis in a concentration-dependent manner. These results suggest that HDL prevent the suicide pathway leading to apoptosis of endothelial cells by decreasing the CPP32-like protease activity and that HDL thus play a protective role against the "response-to-injury" hypothesis of atherogenesis.     

Single neurone responses to tactile stimulation of the heart in the snail,Helix pomatia L.

Summary The electrical activity of the heart nerve and of single neurons in the suboesophageal ganglia were recorded during tactile stimulation of the heart. 15 neurons were identified which responded to heart stimulation by inhibiting or accelerating activity. Cells influenced by heart afferents are scattered in the visceral and in the right and left parietal ganglia.In most of the cases both decrease and increase of cell activity are caused by synaptic potentials, in some cases, however, the neuron is assumed to have a sensory character.The activity of three neurons influenced by heart stimulation was conducted into the heart nerve. These cells are central neurons of a heart-CNS-heart reflex.Some of the neurons located in the right parietal and visceral ganglia have no connection with the mechanoreceptors of the heart. Since their spikes propagate into the heart nerve, they probably take part in the extracardial regulation of heart activity.One of the neurons located in the visceral ganglion (cell V12) sends its axon into the heart nerve. The response of this neuron to heart stimulation was an increase in activity and an inhibition of the heart rate. This is an inhibitory neuron of the extracardial heart regulatory system.     

Alterations in tissue glutathione antioxidant system in streptozotocin-induced diabetic rats

Changes in tissue glutathione antioxidant system in streptozotocin-induced diabetic rats for a period of 15 weeks were examined. Total glutathione level was significantly increased in kidney tissue, but were slightly decreased and increased in liver and heart tissues, respectively. The small changes in total glutathione level in the liver and heart, though not statistically significant, were associated with reciprocal alterations in the activity Of -glutamylcysteine synthetase (GCS). While the GCS activity was not changed in kidney tissue, the activity of -glutathione peroxidase was significantly increased in kidney tissue. Insulin treatment could completely or partly normalize almost all of these changes induced by diabetes. However, the decrease in hepatic glutathione S-transferases activity in diabetic rats was not reversed by the insulin treatment. The ensemble of results suggests that the diabetes-induced alterations in tissue glutathione antioxidant system may possibly reflect an inter-organ antioxidant response to a generalized increase in tissue oxidative stress associated with diabetes.Abbreviations AGES advanced glycosylation end-products - EDTA ethylenediamine tetraacetic acid - GCS -glutamylcysteine synthetase - GlyHb glycated hemoglobin - GPX Se-glutathione peroxidase - GRD glutathione reductase - GSH reduced glutathione - GSSG oxidized glutathione - GST glutathione S-transferases - SSA sulfosalicylic acid - STZ streptozotocin     

Effect of chronic ethanol consumption on emotional stress in the white rat

Chronic pain emotional stress (PES), paired action of the white noise and electric skin stimulation and chronic (during 7 months) ethanol consumption in white rats were shown to act in the same direction. Hypertension, decrease of respiratory rate and increase of Hildebrandt index were observed as a result of PES, ethanol consumption, and especially under PES during ethanol consumption. Ethanol consumption by the animals led to their growth retardation and increase of the spleen and heart mass. Accidental thymus involution was noted both under ethanol consumption and PES. Activation of lipid peroxidation and decrease of superoxide dismutase activity (of its mitochondrial form especially) as well as of Na+,K+-ATP-ase activity were observed in brain homogenates of the rats after PES, while the general ATP-ase activity remained unchanged. An increase of triiodothyronine level and the tendency to thyroxine level increase as well as a decrease of superoxide dismutase activity were observed in the blood serum of these animals. A tendency towards lipid peroxidation level decrease and to brain superoxide dismutase activity increase, as well as blood antioxidation activity increase (evaluated by transferrin and coeruloplasmin contents and by serum superoxide dismutase activity) and a decrease of thyroxine level were observed as a result of ethanol consumption. The mechanisms are discussed of the "anti-stress" action of short-term ethanol consumption and of the action of its chronic consumption, additive to PES.     

Mouse Strain Determines Cardiac Growth Potential

Rationale

The extent of heart disease varies from person to person, suggesting that genetic background is important in pathology. Genetic background is also important when selecting appropriate mouse models to study heart disease. This study examines heart growth as a function of strain, specifically C57BL/6 and DBA/2 mouse strains.

Objective

In this study, we test the hypothesis that two strains of mice, C57BL/6 and DBA/2, will produce varying degrees of heart growth in both physiological and pathological settings.

Methods and Results

Differences in heart dimensions are detectable by echocardiography at 8 weeks of age. Percentages of cardiac progenitor cells (c-kit+ cells) and mononucleated cells were found to be in a higher percentage in DBA/2 mice, and more tri- and quad-nucleated cells were in C57BL/6 mice. Cardiomyocyte turnover shows no significant changes in mitotic activity, however, there is more apoptotic activity in DBA/2 mice. Cardiomyocyte cell size increased with age, but increased more in DBA/2 mice, although percentages of nucleated cells remained the same in both strains. Two-week isoproterenol stimulation showed an increase in heart growth in DBA/2 mice, both at cardiomyocyte and whole heart level. In isoproterenol-treated DBA/2 mice, there was also a greater expression level of the hypertrophy marker, ANF, compared to C57BL/6 mice.

Conclusion

We conclude that the DBA/2 mouse strain has a more immature cardiac phenotype, which correlates to a cardiac protective response to hypertrophy in both physiological and pathological stimulations.     

Effects of adrenaline on the isolated heart of the trout (Salmo gairdneri R.) before and after transfer from fresh water to sea water

1. Adrenaline induces positive inotropic and chronotropic effects on the isolated heart of the trout (Salmo gairdnerii) via the stimulation of beta adrenoreceptors. 2. The effects are relatively more marked in winter than in spring. But there is no seasonal variation as in the cel. The intrinsic reactivity of the heart is not basically modified after a transfer from fresh water to sea water. 3. However, after such a transfer, adrenaline induces an increase of the membrane resting potential which suggests that adrenaline can enhance the activity of the Na/K pump and/or modify the Ca/K balance and could improve the cardiac performances during the "crisis period" following the transfer.     

Modulation of lipoprotein lipase activity in cultured rat mesenchymal heart cells and preadipocytes by dibutyryl cyclic AMP, cholera toxin and 3-isobutyl-1-methylxanthine

We have compared the effects of cellular cyclic AMP modulation on the regulation of lipoprotein lipase in cultures of rat epididymal pad preadipocytes and mesenchymal heart cells. Addition of dibutyryl cyclic AMP (dibutyryl cAMP) or 3-isobutyl-1-methylxanthine (IBMX) to preadipocytes grown in serum-containing culture medium resulted in a progressive decrease in lipoprotein lipase activity released into the culture medium so that at 6-8 h enzyme activity ranged between 20 and 30% of that recovered in the control dishes. Similar short-term (6-8 h) studies of the heart cell cultures showed a variable and much less pronounced depression of lipoprotein lipase activity. Thus, following dibutyryl cAMP and IBMX treatment, lipoprotein lipase activity ranged between 70 and 95% of control values. Incubation for 6 h with cholera toxin was followed by a 4-fold rise in the concentration of cellular cyclic AMP in both types of culture, but while in heart cell cultures enzyme activity was unchanged, lipoprotein lipase activity in preadipocytes decreased to 30% of control value. After 24 h incubation with all three effectors, an increase in lipoprotein lipase activity was seen. In the preadipocytes the increase ranged between 50 and 150% above control value, in the heart cell cultures it was 100-250%. 24-h incubation of heart cell cultures with dibutyryl cAMP resulted in a 6-fold increase of heparin-releasable lipoprotein lipase activity while residual activity was doubled. The rise in surface-bound lipoprotein lipase was evidenced also by an increase in the lipolysis of chylomicron triacylglycerol. In the presence of cycloheximide, the dibutyryl cAMP-induced heparin-releasable and residual lipoprotein lipase activity declined at the same rate as the basal activity. The reason for the difference in response of cultured preadipocytes and heart cells to the effectors during the first 8 h of incubation has not been elucidated, but could be related to a possible absence of hormone-sensitive lipase in the heart cells, and hence in a difference in intracellular metabolism of triacylglycerol. On the other hand, a common mechanism can be postulated for the long-term effect of cyclic AMP on the induction of lipoprotein lipase activity in both types of cultures. It probably involves mRNA and protein synthesis, which culminates in an increase in enzyme activity.     

Changes in β-adrenoceptors in heart failure due to myocardial infarction are attenuated by blockade of renin–angiotensin system

Earlier studies have revealed an improvement of cardiac function in animals with congestive heart failure (CHF) due to myocardial infarction (MI) by treatment with angiotensin converting enzyme (ACE) inhibitors. Since heart failure is also associated with attenuated responses to catecholamines, we examined the effects of imidapril, an ACE inhibitor, on the -adrenoceptor (-AR) signal transduction in the failing heart. Heart failure in rats was induced by occluding the coronary artery, and 3 weeks later the animals were treated with 1 mg/(kg·day) (orally) imidapril for 4 weeks. The animals were assessed for their left ventricular function and inotropic responses to isoproterenol. Cardiomyocytes and crude membranes were isolated from the non-ischemic viable left ventricle and examined for the intracellular concentration of Ca²⁺ [Ca²⁺]_i and -ARs as well as adenylyl cyclase (AC) activity, respectively. Animals with heart failure exhibited depressions in ventricular function and positive inotropic response to isoproterenol as well as isoproterenol-induced increase in [Ca²⁺]_i in cardiomyocytes; these changes were attenuated by imidapril treatment. Both ₁-AR receptor density and isoproterenol-stimulated AC activity were decreased in the failing heart and these alterations were prevented by imidapril treatment. Alterations in cardiac function, positive inotropic effect of isoproterenol, ₁-AR density and isoproterenol-stimulated AC activity in the failing heart were also attenuated by treatment with another ACE inhibitor, enalapril and an angiotensin II receptor antagonist, losartan. The results indicate that imidapril not only attenuates cardiac dysfunction but also prevents changes in -AR signal transduction in CHF due to MI. These beneficial effects are similar to those of enalapril or losartan and thus appear to be due to blockade of the renin–angiotensin system. (Mol Cell Biochem 263: 11–20, 2004)     

Alterations in G-proteins in congestive heart failure in cardiomyopathic (UM-X7.1) hamsters

In order to explain the attenuated sympathetic support during the development of heart failure, the status of -adrenergic mechanisms in the failing myocardium was assessed by employing cardiomyopathic hamsters (155–170 days old) at moderate degree of congestive heart failure. The norepinephrine turnover rate was increased but the norepinephrine content was decreased in cardiomyopathic hearts. The number and the affinity of receptors in the sarcolemmal preparations were not changed in these hearts at moderate stage of congestive heart failure. While the basal adenylyl cyclase activity was not altered in sarcolemma, the stimulation of enzyme activity by NaF, forskolin, Gpp(NH)p or epinephrine was depressed in hearts from these cardiomyopathic hamsters. Since G-proteins are involved in modifying the adenylyl cyclase activity, the functional and bioactivities as well as contents of both Gs and Gi proteins were determined in the cardiomyopathic heart sarcolemma. The functional stimulation of adenylyl cyclase by cholera toxin, which activates Gs proteins, was markedly depressed whereas that by Pertussis toxin, which inhibits Gi proteins, was markedly augmented in cardiomyopathic hearts. The cholera toxin and pertussis toxin catalyzed ADP-ribosylation was increased by 37 and 126%, respectively; this indicated increased bioactivities of both Gs and Gi proteins in experimental preparations. The immunoblot analysis suggested 74 and 124% increase in Gs and Gi contents in failing hearts, respectively. These results suggest that depressed adenylyl cyclase activation in cardiomyopathic hamsters may not only be due to increased content and bioactivity of Gi proteins but the functional uncoupling of Gs proteins from the adenylyl cyclase enzyme may also be involved at this stage of heart failure.     

Isolation of calcium pump system and purification of calcium ion-dependent ATPase from heart muscle.

The procedure for the isolation of the highly active fraction of sarcoplasmic reticulum from pigeon and dog hearts is described. The method is based on the partial loading of heart microsomes with calcium and oxalate ions and the precipitation of loaded vesicles in sucrose and potassium chloride concentration gradients. Preparations obtained possess high activity of Ca2+-dependent ATPase and are also able to accumulate up to 10 mumol Ca2+ per mg protein. Purification of sarcoplasmic reticulum membranes is accompanied by a decrease in concentration of cytochrome a+a3 and an increase in the content of [32P]phosphoenzyme. The basic components in "calcium-oxalate preparation" from hearts are proteins with molecular weights of about 100000 (Ca2+-dependent ATPase) and 55000 Calcium-oxalate preparation from pigeon hearts was used for subsequent purification of Ca2+-dependent ATPase. Specific activity of purified enzyme from pigeon hearts is 12-16 mumol Pi/min per mg protein. Enzyme activity of purified Ca2+-dependent ATPase is inhibited by EGTA and is not sensitive to azide, 2,4-dinitrophenol and ouabain. The data obtained demonstrate the similarity of calcium pump systems and Ca2+-dependent ATPases isolated from heart and skeletal muscles.