Body adaptation to stress exposure enhances cardiac resistance to adrenotoxic damage

Models of adrenergic arrhythmias were produced on isolated rat heart under the adrenalin concentration in the perfusion solution of 5.10(-5) M. The rhythm disturbances were accompanied by a pronounced depression of contractile function. It was shown that preliminary adaptation of animals to short-term stress exposures reduced the duration of arrhythmias more than sixfold the contractile function, being maintained at a higher level than in control. The adaptation cardioprotective effect was compared with the effects of adaptation and propranolol appeared similar.     

Interrelations between oxidative stress and calcineurin in the attenuation of cardiac apoptosis by eugenol

In view of the known involvement of oxidative stress and calcineurin (Ca²⁺-calmodulin dependent protein phosphatase) in β-Adrenergic stimulated events, we examined the influence of eugenol (an antioxidant generally regarded as safe by the Food and Agricultural Organization of the United Nations) on isoproterenol-induced apoptosis in neonatal cardiomyocytes. In comparison to unstimulated controls, cardiomyocytes stimulated with 50 μM isoproterenol for 48 h demonstrated (a) increased intracellular Ca²⁺ levels (b) oxidative stress involving enhanced reactive oxygen species, decreased GSH/GSSG ratio, enhanced lipid peroxidation, increased activities of superoxide dismutase and glutathione peroxidase (c) apoptosis, evidenced by increased number of annexin V/TUNEL positive cells, enhanced membrane fluidity, decreased mitochondrial membrane potential, increased activities of caspase 3 and 9 along with (d) increased calcineurin activity. Pre-incubation of cardiomyocytes with 100 μM eugenol for 1 h, followed by isoproterenol treatment for 48 h, led to reversal of enhanced intracellular Ca²⁺ levels, oxidative stress, calcineurin activation and apoptosis caused by isoproterenol. In addition, similar treatment of cardiomyocytes with 10 nM FK506, a calcineurin inhibitor, could also attenuate isoproterenol-induced apoptosis. These results indicate the beneficial effects of eugenol in preventing cardiomyocyte apoptosis.     

Interrelations between hydraulic and mechanical stress adaptations in woody plants

The fields of plant water relations and plant biomechanics have traditionally been studied separately even though often the same tissues are responsible for water transport and mechanical support. There is now increasing evidence that hydraulic and mechanical adaptations may influence one another. We studied the changes in the hydraulic and mechanical properties of the wood along lateral roots of two species of buttressed trees. In these roots, the mechanical contstraints quantified by strain measurements are known to decrease distally. Further, we investigated the effect of mechanical loading on the vessel anatomy in these and four other species of tropical trees. We found that as the strain decreased, the wood became progressively less stiff and strong but the conductivity increased exponentially. This was reflected in that adaptations towards re-enforcing mechanically loaded areas resulted in xylem with fewer and smaller vessels. In addition a controlled growth experiment on three tree species showed that drought adaptation may results in plants with stronger and stiffer tissue. Our results indicate that hydraulic and mechanical stress adaptations may be interrelated, and so support recent studied suggesting that physiological responses are complex balances rather than pure optimisations.Key words: conductivity, modulus of elasticity, strain, tree ecophysiology, tropical trees, wood anatomy, yield stressIt is well known that the woody tissue of plants is responsible for carrying out several functions simultaneously, of which the two most important may be water transport and mechanical support. In spite of this, the fields of plant water relations and plant biomechanics have traditionally been studied separately (however, see refs. ^1–4). An increasing number of studies now indicate that there may be interrelations between hydraulic and mechanical stress adaptations, both in the form of positive interactions and trade-offs. In the former case, adaptations with respect to one of the two stresses positively affect the plants ability to withstand the other. Drought adaptation, for instance, is associated with an increase in the density of the tissue, which may result in stiffer and stronger wood.^5,6 Further, increasing the transectional area of the sapwood increases the conductivity as well as the rigidity of the plant and may occur as an adaptation to either drought- or mechanical stress.^7,8 In such cases, because of the importance of hydraulic sufficiency as well as adequate mechanical support, biomass must be partitioned to allow for both functions simultaneously even if this results in a surplus allocation with respect to one. In the case of trade-offs, the hydraulic or mechanical adaptations are detrimental to the plants'' capabilities with respect to the other. Within the woody tissue, for instance, larger and more numerous vessels increase the conductivity but may weaken the wood.^1–3,9–11 Analogously, hydraulic optimisation dictates an increase in the transectional sapwood area up though the plant, so that the summed area of all branches at a given height would be greater than that of the trunk¹² but mechanical optimisation a decrease.¹³ In the case of physiological parameters within which there are trade-offs, achieving adequate design whilst minimising biomass allocation becomes complex,⁴ and a number of possible but less optimal solutions exist.In our study,¹⁴ we looked at how mechanical as well as hydraulic parameters changed along the lateral roots of two tropical tree species, Tachigali melinonii and Xylopia nitida, both of which produce buttress roots. Along the roots of these species there is a strong distal decrease in the magnitude of the locally supported mechanical loads,¹⁵ making them ideal model organisms for investigating mechanical adaptation of the tissue and the impact this has on hydraulic parameters. We measured the density, conductivity, strength, stiffness, sapwood area and second moment of area at various points distally along the roots as well as in the lower trunk, and compared the values to those for strain. In both species, the strength and stiffness of the tissue decreased distally along the roots as the strain dropped, and the conductivity concurrently increased exponentially (Fig. 1). This appeared related to changes in the density of the wood; in both species, the density increased towards the bole and was positively correlated with mechanical properties but negatively with conductivity. As in previous studies, the distal most roots had a higher conductivity and lower stiffness and strength than that of the trunk. The proximal roots, however, had a lower conductivity but a greater strength and density. This indicates that the general pattern that roots have a higher conductivity than the stem cannot be explained by the water potential gradient from the soil to the leaves as often assumed, but instead by the differing mechanical requirements on these structures.Open in a separate windowFigure 1The modulus of elasticity in bending, E, (solid lines) and the specific conductivity, K_s, (dashed lines) of the woody tissue of the lateral roots shown as a function of the distance from the bole. The trend-lines are shown for the buttressed tree species Tachigali melinonii (black) and Xylopia nitida (grey), and are based on data presented in Christensen-Dalsgaard, et al, 2007a.These hydraulic and mechanical adaptations were well in accordance with anatomical adaptations seen for these as well as four other species from the same area representing two different rooting morphologies, for which the strain patterns differ. We found that the vessels were significantly smaller and less numerous in the xylem tissue of highly mechanically loaded compared to less loaded sections of the tree¹⁵ (Fig. 2). Further, the generally observed pattern^16,17 that vessel size increases radially from the pit to the bark was not observed throughout the structure.¹⁸ In the proximal parts of the buttress roots, which are highly mechanically loaded throughout growth and development, the vessels maintained the small size found at the pith throughout the transect. In the distal parts of the buttress roots, in which the mechanical loading increases during growth, the vessels decreased rather than increased in size from the pith to the bark.¹⁸ Since the adaptation of the xylem tissue towards re-enforcing highly strained areas appear associated with changes in the vessel anatomy reducing the conductivity, radial changes in vessel size may not only be a function of cambial ageing, but also influenced by changes in stresses during growth.Open in a separate windowFigure 2Tissue sections from the trunk and roots of the buttressed tree species Xylopia nitida, left, and the taproot anchored Oxandra asbeckii, right. All tissue sections are imaged at the same magnification; the width of each image is 4, 6 mm. In O. asbeckii, where the main rigid element resisting overturning is provided by the taproot and the lower bole, the trunk has smaller and fewer vessels than either of the root sections, as often described in litterature. In buttressed species such as X. nitida, on the other hand, where the area subjected to the greatest longitudinal strains and stresses is found in the proximal part of the buttress roots (marked in grey), this part of the root system is instead associated with fewer and smaller vessels than the trunk.In addition to hydraulic effects of mechanical adaptations, the converse may occur; hydraulic adaptations could affect the mechanical properties of the tissue. Drought adapted plants have a greater resistance to cavitation,^19,20 which appears related to an increased relative thickness of the conduit or the fibre cell walls,^5,21 and so an increased wood density.^5,22 However, since the mechanical properties are determined by the micro fibril angle (MFA) of the S2 cell wall layer as well as density,²³ the data from the few studies measuring the mechanical effects of hydraulic adaptation have not found consistent effects.^24,25 In these studies, complex natural systems were investigated making it difficult to distinguish between various climatic effects. We therefore grew seedlings from the three tree species Ochroma lagopus, Acacia karroo and Betula pendula under well-watered and droughted conditions, respectively, and measured the effect on the modulus of elasticity, the yield stress and the density (unpublished results). The stems of the droughted plants had a higher stiffness and strength than that of the well-watered plants. Only in O. lagopus, however, did the stems of the droughted seedlings have denser tissue than that of the well-watered seedlings; in B. pendula and A. karroo the mechanical differences were probably due to adaptations in the MFA instead. This was supported by that the density/elasticity ratio, which may be a good indicator of the MFA,^23,26 was significantly higher in the well-watered than in the droughted plants.Our work adds to the growing body of evidence indicating that there may be interrelations between hydraulic and mechanical stress adaptations.^{1–3,5,9–12,25} Modifications of the xylem towards mechanically reinforcing stressed or strained areas simultaneously impacted the conductive physiology of the trees studied, and drought adaptations resulted in stiffer and stronger tissue. This provides further evidence that in order to fully understand plant physiology and ecology it is necessary to consider the various functions of wood simultaneously and attempt to unravel causal relationships between e.g., the hydraulic and mechanical functioning of the tissue. Rather than being a matter of simple optimisations, adaptations towards one environmental stress will affect how plants adapt to the others. Because of the complexity of this balance, however, interrelations between parameters are not always found. For instance, mechanical strengthening due to hydraulic adaptations could reduce hydraulic effects of mechanical stresses; trees growing in climates with winter frost may be stronger due to larger amounts of sap- or heart wood and drought adaptation may result in a stiffer and stronger plant.^21,24,27 This could explain why the relatively clear trade-off between hydraulic and mechanical parameters found in this and other studies have not always been found in non-tropical species.^{21,24,27–29} Deepening our knowledge on how multi-factor adaptation balances are affected by climatic conditions and the signalling processes involved in these complex processes would aid our understanding of ecophysiological responses in plants.     

Sex differences in adrenocortical sensitivity and resistance to cerebrovascular damage in rats under strong stress]

Dynamics of changes in adrenal and plasma corticosterone and the development of cerebrovascular lesions were studied in both male and female rats, exposed to strong stress (combined immobilization and intermittent found sound for 2 hours). Plasma corticosterone levels in stressed females were 460% and 660% of the control values when measured on stress minute 10 and 120. The corresponding values in male rats were 220% and 360%. The stress-induced dilatation of brain vessels and the increases in vascular permeability were less pronounced in females than in males, when studied 0.1 and 24 hours after termination of stress. The number of brain perivascular haemorrhages was markedly reduced in females compared with males. It is supposed that higher resistance to stress-induced cerebrovascular lesions in females may be attributed to higher functional reserves of steroidogenesis.     

Interrelations between the sympathoadrenal system,adrenal cortex,and autonomic tone in seven- to nine-year-old children

Comprehensive study of the functional state of the sympathoadrenal system (SAS) and adrenal cortex (AC) and the specific features of the autonomic regulation of the cardiac rhythm revealed close correlations between the excretion of catecholamines (CAs) and androgens, on the one hand, and the initial autonomic tone (IAT) of the cardiovascular system of children, on the other hand. Most schoolchildren of both sexes with a predominant dependence of their cardiac rhythm on sympathetic influences were shown to excrete more noradrenaline (NA), 17-hydroxycorticosteroids, and 17-ketosteroids and less dopamine than their normotonic and vagotonic counterparts, which was accompanied by an increase in the NA-to-adrenaline ratio. In contrast, eight-and nine-year-old girls exhibited a relatively decreased activity of glucocorticoid functions of the AC associated with sympathicotonia. A local static effort performed as a functional test caused similarly directed changes in the functional states of the SAS and AC in a manner dependent on the child’s IAT, age, and sex. In the states of sympathicotonia or normotonia, nine-year-old girls exhibited a decrease in the excretion of CAs and DOPA or their insignificant increase accompanied by strengthening of the functional activity of the AC, especially of its androgen function. This may be interpreted as a manifestation of specific neuroendocrine interrelations in the adaptive mechanisms of nine-year-old girls and a higher stability of the pituitary-adrenal system, which controls metabolic processes in the growing body. In contrast, in normotonic and vagotonic seven-year-old boys (as well as in sympathicotonic eight-year-old boys), the local static effort revealed simultaneous decreases in the reserve potentials of the SAS and AC, probably caused by fatigue and asthenization of these children during their schoolwork.     

3D-model of adult cardiac stem cells promotes cardiac differentiation and resistance to oxidative stress

The regenerative inadequacy of the injured myocardium leads to adverse remodeling, cardiac dysfunction, and heart disease. Stem cell-replacement of damaged myocardium faces major challenges such as inappropriate differentiation, cellular uncoupling, scar formation, and accelerated apoptosis of transplanted cells. These challenges can be met by engineering an in vitro system for delivering stem cells capable of cardiac differentiation, tissue integration, and resistance to oxidative stress. In this study, we describe the formation of three-dimensional (3D) cell aggregates ("cardiospheres") by putative stem cells isolated from adult dog myocardium using poly-L-ornithine. De novo formation of cardiospheres in growth factor-containing medium occurred over a period of 2-3 weeks, but accelerated to 2-3 days when seeded on poly-L-ornithine. Older cardiospheres developed foci of "beating" cells upon co-culture with rat neonatal cardiomyocytes. Cardiospheres contained cells that exhibited characteristics of undifferentiated cells; differentiating cardiomyocytes with organized contractile machinery; and vascular cells capable of forming "vessel-like" networks. They exhibited strong resistance to elevated concentrations of hydrogen peroxide in culture and survived subcutaneous injections without undergoing neoplastic transformation up to 3 weeks post-transplantation. These findings suggest that cardiospheres are potentially useful for delivering functional stem cells to the damaged heart.     

The contribution of DNA repair and antioxidants in determining cell type-specific resistance to oxidative stress

The aims of this study were; (i) to elucidate the mechanisms involved in determining cell type-specific responses to oxidative stress and (ii) to test the hypothesis that cell types which are subjected to high oxidative burdens in vivo, have greater oxidative stress resistance. Cultures of the retinal pigment epithelium (RPE), corneal fibroblasts, alveolar type II epithelium and skin epidermal cells were studied. Cellular sensitivity to H2O2 was determined by the MTT assay. Cellular antioxidant status (CuZnSOD, MnSOD, GPX, CAT) was analyzed with enzymatic assays and the susceptibility and repair capacities of nuclear and mitochondrial genomes were assessed by QPCR. Cell type-specific responses to H2O2 were observed. The RPE had the greatest resistance to oxidative stress (P>0.05; compared to all other cell types) followed by the corneal fibroblasts (P < 0.05; compared to skin and lung cells). The oxidative tolerance of the RPE coincided with greater CuZnSOD, GPX and CAT enzymatic activity (P < 0.05; compared to other cells). The RPE and corneal fibroblasts both had up-regulated nDNA repair post-treatment (P < 0.05; compared to all other cells). In summary, variations in the synergistic interplay between enzymatic antioxidants and nDNA repair have important roles in influencing cell type-specific vulnerability to oxidative stress. Furthermore, cells located in highly oxidizing microenvironments appear to have more efficient oxidative defence and repair mechanisms.     

The effect of chemical damage to the adrenal cortex on its ontogenetic development]

We studied adrenal gland of rats at the age of 1 month, which underwent injections of dioxin-preparations during a week. In 1, 6, 12 days; 1, 3, 5, 5, 7, 13 months adrenal gland mass, adrenal cortex size, adrenocorticocytes number, 3B-ol-steroid dehydrogenase and succinate dehydrogenase activities of the experimental animals differed greatly from that of the control. It was found that chemical damage of the gland at an early stage changes it greatly during the following ontogenic development.     

Primary response mechanisms of the adrenal cortex in dogs to pain stress]

The adrenal cortex of dogs shows a drop in the glucocorticoid content 10--15 sec after the pain action in the presence of the free cholesterol level increase and its esterified form drop. The concentrations of hormones in the blood falls chiefly at the expense of protein bound hydrocortisone. The subsequent phase of the reaction (after 30--60 sec) is characterized by a considerable accumulation of the hormones by the gland. The level of free glucocorticoids significantly increases, the initial ratio of hydrocortisone and cortisone restores, and transcortin depot is filled up. The role of the adrenal and transcortine depot in realization of feedback mechanisms under stress is discussed.     

Muscle pain perception and sympathetic nerve activity to exercise during opioid modulation

The purpose of this experiment was to examine the effects of the endogenous opioid system on forearm muscle pain and muscle sympathetic nerve activity (MSNA) during dynamic fatiguing exercise. Twelve college-age men (24 +/- 4 yr) performed graded (1-min stages; 30 contractions/min) handgrip to fatigue 1 h after the ingestion of either 60 mg codeine, 50 mg naltrexone, or placebo. Pain (0-10 scale) and exertion (0-10 and 6-20 scales) intensities were measured during the last 15 s of each minute of exercise and every 15 s during recovery. MSNA was measured continuously from the peroneal nerve in the left leg. Pain threshold occurred earlier [1.8 +/- 1, 2. 2 +/- 1, 2.2 +/- 1 J: codeine, naltrexone, and placebo, respectively] and was associated with a lower rating of perceived exertion (RPE) (2.7 +/- 2, 3.6 +/- 2, 3.8 +/- 2: codeine, naltrexone, and placebo, respectively) in the codeine condition compared with either the naltrexone or placebo conditions. There were no main effects (i.e., drugs) or interaction (i.e., drugs x time) for either forearm muscle pain or RPE during exercise [pain: F (2, 22) = 0.69, P = 0.51]. There was no effect of drug on MSNA, heart rate, or blood pressure during baseline, exercise, or recovery. Peak exercise MSNA responses were 21 +/- 1, 21 +/- 2.0, and 21 +/- 2.0 bursts/30 s for codeine, naltrexone, and placebo conditions, respectively. Peak mean arterial pressure responses were 135 +/- 4, 131 +/- 3, and 132 +/- 4 mmHg for codeine, naltrexone, and placebo conditions, respectively. It is concluded that neither 60 mg codeine nor 50 mg naltrexone has an effect on forearm muscle pain, exertion, or MSNA during high- intensity handgrip to fatigue.     

Relation between QT interval variability and cardiac sympathetic activity in hypertension

Elevated QT interval variability is a predictor of malignant ventricular arrhythmia, but the underlying mechanisms are incompletely understood. A recent study in dogs with pacing-induced heart failure suggests that QT variability is linked to cardiac sympathetic nerve activity. The aim of this study was to determine whether increased cardiac sympathetic activity is associated with increased beat-to-beat QT interval variability in patients with essential hypertension. We recorded resting norepinephrine (NE) spillover into the coronary sinus and single-lead, short-term, high-resolution, body-surface ECG in 23 patients with essential hypertension and 9 normotensive control subjects. To assess beat-to-beat QT interval variability, we calculated the overall QT variability (QTVN) as well as the QT variability index (QTVi). Cardiac NE spillover (12.2 ± 6.5 vs. 20.7 ± 14.7, P = 0.03) and QTVi (-1.75 ± 0.36 vs. -1.42 ± 0.50, P = 0.05) were significantly increased in hypertensive patients compared with normotensive subjects. QTVN was significantly correlated with cardiac NE spillover (r(2) = 0.31, P = 0.001), with RR variability (r(2) = 0.20, P = 0.008), and with systolic blood pressure (r(2) = 0.16, P = 0.02). Linear regression analysis identified the former two as independent predictors of QTVN. In conclusion, elevated repolarization lability is directly associated with sympathetic cardiac activation in patients with essential hypertension.     

Variability of hemodynamic parameters and resistance to stress damage in rats of different strains

Total power of heart rate variability and baroreflex sensitivity were significantly smaller in the August rats than in the Wistar rats, but adrenal and plasma catecholamine contents were considerably higher in the former ones. 1 hour after stress (30 min in cold water), plasma catecholamine was increased 2-fold in Wistar rats, while in August rats the adrenaline concentration increased only by 58% and the were no changes in noradrenaline content. At the same time, activation of catecholamine metabolism in the adrenal glands was similar in both groups. The oxidative stress induced by hydrogen peroxide depressed the contractile function of isolated heart in the August rats to a smaller extent as compared to Wistar rats, control ones and after the cold-water stress. This effect correlated with more pronounced stability ofantioxidant enzymes in the August rats. It seems that the greater resistance to stress damage in the August rats is mediated by enhanced power of defense mechanisms both at systemic and cellular levels.     

Positive correlation between mammalian life span and cellular resistance to stress

Identifying the mechanisms determining species-specific life spans is a central challenge in understanding the biology of aging. Cellular stresses produce damage, that may accumulate and cause aging. Evolution theory predicts that long-lived species secure their longevity through investment in a more durable soma, including enhanced cellular resistance to stress. To investigate whether cells from long-lived species have better mechanisms to cope with oxidative and non-oxidative stress, we compared cellular resistance of primary skin fibroblasts from eight mammalian species with a range of life spans. Cell survival was measured by the thymidine incorporation assay following stresses induced by paraquat, hydrogen peroxide, tert-butyl hydroperoxide, sodium arsenite and alkaline pH (sodium hydroxide). Significant positive correlations between cell LD90 and maximum life span were found for all these stresses. Similar results were obtained when cell survival was measured by the MTT assay, and when lymphocytes from different species were compared. Cellular resistance to a variety of oxidative and non-oxidative stresses was positively correlated with mammalian longevity. Our results support the concept that the gene network regulating the cellular response to stress is functionally important in aging and longevity.     

Static interaction between muscle mechanoreflex and arterial baroreflex in determining efferent sympathetic nerve activity

Elucidation of the interaction between the muscle mechanoreflex and the arterial baroreflex is essential for better understanding of sympathetic regulation during exercise. We characterized the effects of these two reflexes on sympathetic nerve activity (SNA) in anesthetized rabbits (n = 7). Under open-loop baroreflex conditions, we recorded renal SNA at carotid sinus pressure (CSP) of 40, 80, 120, or 160 mmHg while passively stretching the hindlimb muscle at muscle tension (MT) of 0, 2, 4, or 6 kg. The MT-SNA relationship at CSP of 40 mmHg approximated a straight line. Increase in CSP from 40 to 120 and 160 mmHg shifted the MT-SNA relationship downward and reduced the response range (the difference between maximum and minimum SNA) to 43 +/- 10% and 19 +/- 6%, respectively (P < 0.01). The CSP-SNA relationship at MT of 0 kg approximated a sigmoid curve. Increase in MT from 0 to 2, 4, and 6 kg shifted the CSP-SNA relationship upward and extended the response range to 133 +/- 8%, 156 +/- 14%, and 178 +/- 15%, respectively (P < 0.01). A model of algebraic summation, i.e., parallel shift, with a threshold of SNA functionally reproduced the interaction of the two reflexes (y = 1.00x - 0.01; r(2) = 0.991, root mean square = 2.6% between estimated and measured SNA). In conclusion, the response ranges of SNA to baroreceptor and muscle mechanoreceptor input changed in a manner that could be explained by a parallel shift with threshold.     

Organization of reflex sympathetic influence on rate and force of cardiac contraction]

In acute experiments on 21 cats it was proved that the change of afferent impulse on vagus nerves by means of either freeze-block or electrostimulation of their central ends results in differential reflex influences on rhythm and force of the cardiac contractions caused by sympathetic nervous system. The cut of the lower cardiac nerves may cause 'break-up' of the observed reflex, removing or inverting its ino- or chronotropy component. The given phenomenon was revealed in the experiments with high arterial pressure and with absence of tonic chronotropy influences of the left lower cardiac nerve.