Effect of hydrocortisone on peripheral blood phagocytic cells under beta-adrenoreceptors blockade

The effect of hydrocortisone (50 mg/kg body wt i.p.) under beta-adrenergic receptors blockade (four subcutaneous injections of propranolol in single dose of 5 mg/kg body wt with 3 h interval) on phagocytic activity and oxygen dependent microbicidal activity in NBT-test of peripheral blood phagocytic cells in male Wistar rats was investigated. It was established that hydrocortisone stimulated neutrophil phagocytic activity through 6, 24 and 48 h after hormone injection and decreased oxygen-dependent microbicidal activity of phagocytic cells in NBT-test. Hydrocortisone in vitro (500 ng/ml) decreased neutrophil phagocytic activity that indicated on realization of stimulating effect of hydrocortisone in vivo through complex of other indirect mechanisms. Administration of hydrocortisone led to depression of eosinophil phagocytosis and lesser decrease in monocyte phagocytic activity. Hydrocortisone effects were significantly modified under blockade of beta-adrenoceptors that indicated on its mediation by endogenous catecholamines through modulation of beta-adrenoceptor expression.     

Prevention of stress-induced disorders of myocardial contractile function by using sparing adaptation to short-term stress effects

Adaptation to repeated short-term stress is known to prevent to a considerable extent the depression of the myocardial contractile function which usually develops under long-term stress. But the adaptation itself has a "cost", i. e. it results in limited but significant disturbances of myocardial contractile function. The present review documents the method of adaptation involving few actions with prolonged intervals between them. It has been established that such an adaptation per se does not induce any disturbances of contractile function. At the same time it prevents completely the depression of contractile function caused by stress.     

Antioxidant metallothionein alleviates endoplasmic reticulum stress-induced myocardial apoptosis and contractile dysfunction

Abstract

Aims. Endoplasmic reticulum (ER) stress exerts myocardial oxidative stress, apoptosis, and contractile anomalies, although the precise interplay between ER stress and apoptosis remains elusive. This study was designed to examine the impact of the cysteine-rich free radical scavenger metallothionein on ER stress-induced myocardial contractile defect and underlying mechanisms. Methods and results. Wild-type friendly virus B and transgenic mice with cardiac-specific overexpression of metallothionein were challenged with the ER stress inducer tunicamycin (1 mg/kg, intraperitoneal, 48 h) prior to the assessment of myocardial function, oxidative stress, and apoptosis. Our results revealed that tunicamycin promoted cardiac remodeling (enlarged left ventricular end systolic/diastolic diameters with little changes in left ventricular wall thickness), suppressed fractional shortening and cardiomyocyte contractile function, elevated resting Ca²⁺, decreased stimulated Ca²⁺ release, prolonged intracellular Ca²⁺ clearance, and downregulated sarco(endo)plasmic reticulum Ca²⁺-ATPase levels, the effects of which were negated by metallothionein. Treatment with tunicamycin caused cardiomyocyte mitochondrial injury, as evidenced by decreased mitochondrial membrane potential (??m, assessed by JC-1 staining), the effect of which was negated by the antioxidant. Moreover, tunicamycin challenge dramatically facilitated myocardial apoptosis as manifested by increased Bax, caspase 9, and caspase 12 protein levels, as well as elevated caspase 3 activity. Interestingly, metallothionein transgene significantly alleviated tunicamycin-induced myocardial apoptosis. Conclusion. Taken together, our data favor a beneficial effect of metallothionein against ER stress-induced cardiac dysfunction possibly associated with attenuation of myocardial apoptosis.     

Pharmacokinetic analysis of alpha- and beta-adrenoreceptors in the chick embryo amnion

Following a stimulation with acetylcholine, the beta-adrenergic agonists adrenaline (A), noradrenaline (NA), isoproterenol (Iso) and salbutamol (Sal) induced a concentration-dependent decrease in the tone and (or) rate of amnion contraction with EC50 ISO < NA < A < Sal. Metaprolol, a specific beta 1-antagonist, induced a rightward shift in the dose-response curves of Iso, NA and A, whereas beta-antagonist butoxamine was ineffective. pA2 values for beta-antagonists were propranolol 8.3, metoprolol 7.0, butoxamine 5.6. EC50 values of alpha-adrenergic agonists form a sequence: clonidine < NA < methoxamine < phenylephrine. Specific alpha-antagonists yohimbine and idazoxan were found to antagonise competitively the effects of NA. The data obtained characterize the adrenergic receptors mediating stimulation of amniotic contractile activity as alpha 2-adrenergic receptors. Inhibition of contractile receptors in amnion is mainly mediated by beta 1-adrenergic receptor activation.     

Mitotic activity of regenerating rat liver following stimulation with alpha- and beta-adrenoreceptors

A study was made of the effect of stimulating alpha- and beta-adrenoreceptors on the mitotic activity of the rat regenerating liver following resection. Mesaton, a stimulator of alpha-adrenoreceptors, and isadrin, a stimulator of beta-adrenoreceptors, in a dose of 0.2 mg/kg were injected one hour before liver resection or 30 min, 8 and 24 h after operation. In all experimental groups, mesaton gave rise to an increase in the mitotic index without lowering the coefficient of the mitotic phases. The least pronounced stimulating effect was attained when mesaton was injected 9 hours after partial hepatectomy. Isadrin reduced the mitotic activity as judged from the decrease of the coefficient of the phases and augmentation of the number of binuclear cells. The experiments confirmed a previously advanced assumption that stimulation of alpha-adrenoreceptors favours while that of beta-adrenoreceptors reduces cell proliferation.     

Effect of stress-induced lipid peroxidation on functions of rat peritoneal macrophages

The aim of the present study was to investigate the effects of stress-induced lipid peroxidation on macrophages' functions. Animals were subjected to 4 h immobilization at 4 degrees C in restraining devices. The peritoneal macrophages obtained from rats exposed to cold and restraint stress exhibited an increase in lipid peroxidation and a decline of chemotaxis and phagocytosis compared with control rats. After supplementation with vitamin E, the increment in thiobarbituric acid reactive substances (TBARS) content as the oxidative stress marker and the decline of chemotaxis and phagocytosis in peritoneal macrophages observed during cold-restraint stress was significantly removed. No significant change in catalase activity of peritoneal macrophages was observed in groups exposed to cold-restraint stress and treated with vitamin E. These findings indicate that phagocytic and chemotactic capacities of peritoneal macrophages are decreased by cold-restraint stress and this effect of stress may be related to lipid peroxidation.     

Thiol reactivity and the molecular individuality of alpha- and beta-adrenoreceptors in rat liver plasma membranes.

Whether or not alpha- and beta-adrenoreceptors are non-identical binding sites on the same protein is still an open question. We investigated the effects of sulfhydryl reagents and dithiothreitol on the binding of [3H]dihydroalprenolol and [3H]dihydroergocryptine to beta- and alpha-adrenoreceptors of rat liver plasma membranes. Dithiothreitol inhibited the binding of [3H]dihydroalprenolol to the beta-adrenoreceptor, whereas it had no effect on the specific binding of [3H]dihydroergocryptine to the alpha-adrenoreceptor. In contrast, mersalyl, a mercurial SH reagent, readily blocked the alpha-adrenoreceptor and, although to a lesser extent the beta-adrenoreceptor. The interaction of mersalyl with the alpha-adrenoreceptors was almost instantaneous. In contrast, under the same experimental conditions, the inactivation of the beta-adrenoreceptors was much slower (t 1/2 : 7 min). Finally, a marked difference in the accessibility of the SH groups to mersalyl was observed between the alpha- and beta-adrenoreceptors. The presence of 15 microM (-)-epinephrine or 1.5 microM phentolamine was sufficient to prevent the blockade of the alpha-adrenoreceptor by mersalyl, but inactivation of the beta-adrenoreceptor by mersalyl was not modified by 500 microM (-)-epinephrine and was only slightly decreased by 50 microM (-)-propranolol. Thus, the alpha- and beta-adrenoreceptors from rat liver plasma membranes exhibited biochemical differences which may be interpreted in favor of their molecular individuality.     

Effect of lysosomal enzymes on myocardial electrical and contractile activity in burn shock

Marked depression of the amplitude of isometric contractions of myocardial preparations, which was induced by lysosomal enzymes from the liver of control animals, was demonstrated in isolated rabbit papillary muscles. The decrease of contractility was not accompanied by remarkable changes in the amplitude or in the duration of intracellular action potentials. The negative inotropic action of lysosomal enzymes was similar to that of blood plasma of the burnt animals. Based on the appearance and subsequent activation of lysosomal enzymes in blood of the animals by the 20th to 60th min after thermal injury it is suggested that lysosomal enzymes might be one of factors that depress myocardial contractility in burn shock.     

Role of alpha- and beta-adrenoreceptors in rat monocyte/macrophage function at rest and acute exercise

Previous studies from our laboratory have demonstrated that a single bout of moderate exercise stimulates macrophage function, increasing phagocytic capacity, and production of hydrogen peroxide and nitric oxide (NO˙) through nuclear factor kappa B activation. In this work, we investigated the role of α- and β-adrenoreceptors on the function of monocyte/macrophages during rest and exercise. Adult male Wistar rats were i.p. administered (100 μL/100 g) with specific adrenergic antagonists before an acute moderate exercise bout: prazosin (α₁-specific antagonist 2 mg/kg), propranolol (unspecific β_1/β₂ antagonist 10 mg/kg), double blockade (α₁ and β_1/β₂), or phosphate-buffered saline (control). Acute exercise consisted in a single swimming session of moderate intensity (5 % body weight overload on the chest) for 60 min. Control groups (rest) received the same antagonists and were killed 60 min after drug administration. Exercise increased phagocytic capacity (1.7-fold, p?<?0.05), NO˙ production (5.24 fold, p?<?0.001), and inducible nitric oxide synthase (NOS2) expression (by 58.1 %), thus suggesting macrophage activation. The β-adrenoreceptor blockade did not change this behavior. In resting animals, α₁ antagonist, as well as the double (α₁/β) blockade, however, further increased phagocytic capacity (by up to 261 %, p?<?0.001), NO˙ production (by up to 328 %, p?<?0.001), and the expressions of NOS2 (by 182 %, p?<?0.001) and HSP70 (by 42.5 %, p?<?0.01) suggesting a tonic inhibitory effect of α₁ stimulation on macrophage activation. In exercised animals, α₁-blockade showed similar enhancing effect on phagocytic indices and expressions of NOS and HSP70, particularly in double-blocked groups, although NO˙ production was found to be reduced in exercised animals submitted to both α- and β-blockade. Redox (glutathione) status and lipoperoxidation were evaluated in all test groups and approximately paralleled macrophage NO˙ production. We suggest the prevalence of a peripheral α₁-adrenoreceptor inhibitory tonus that limits macrophage responsiveness but operates differently after physical exercise.     

Prevention of stress-induced disorders of myocardial Na, K-ATPase activity using adaptation to short-term stress

It was shown that adaptation to short-term emotional-painful stresses prevented both the decline in the activity and the increase in thermal denaturation rate of Na,K-ATPase in sarcolemmal vesicles isolated from the rat myocardium exposed to prolonged stress. The role of Na-pump damage in the disturbance of the electrical stability of the heart and the development of stress-induced arrhythmia is discussed.     

Noradrenaline and its end metabolite 3-methoxy-4-hydroxyphenylglycol inhibit lymphocyte chemotaxis: Role of alpha- and beta-adrenoreceptors

The capacity of noradrenaline (NA) and its end metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) to modulate the chemotaxis of lymphocytes from a primary immunocompetent organ (thymus) and a secondary one (spleen) was investigated over a range of concentrations from 10^–12 M to 10^–5 M. Lymphocyte chemotaxis was evaluated in a Boyden chamber. The results indicated that 10^–5 M of NA inhibits the chemotaxis of lymphocytes from both the immunocompetent organs studied, and that this effect is blocked by either propranolol (10^–6 M) or phentolamine (10^–5 M). Similarly, 10^–5 M of MHPG induced a decrease in the chemotaxis capacity of the lymphocytes. In conclusion, high physiological concentrations of NA and its end metabolite modulate the mobility of lymphocytes, and the participation of both alpha and beta adrenoreceptors is necessary, showing a new aspect of neuroimmune interactions.     

The short-term and long-term effects of gamma-irradiation on the inotropic reaction of the myocardium during the activation of alpha- and beta-adrenoreceptors

The contractile function of myocardium was impaired and its inotropic response to stimulation of alpha- and beta-adrenoreceptors decreased at early times (1-30 days) following whole-body gamma-irradiation with a dose of 1.0 Gy. Six months after irradiation the response of the isolated myocardium to stimulation of adrenoreceptors increased to exceed that of intact animals. In a year the reactivity of the myocardium towards alpha-adrenoreceptor agonists remained high and its sensitivity of phenylephrine hydrochloride increased considerably; the response to beta-adrenoreceptor agonists was virtually absent.     

Prevention of cardiac contractile function disorders during prolonged stress by preliminary adaptation to short-term stress exposure

Studies of contractile function of an isolated right auricle in Wistar rats have demonstrated that long-term immobilization stress (fixation in the lying position for 6 h) results in the decreased extensibility of the auricle and pronounced depression of the developed tension. Preliminary adaptation of the animals to short-term immobilization stress (daily fixation in the lying position for 1 h over 10 days) per se insignificantly affects the extensibility and contractile function of the auricle but in effect it reduces its adrenoreactivity and completely prevents the post-stressor rigidity of the auricle and its function abnormality after long-term stress.     

Effect of various reperfusion regimens on the recovery of myocardial contractile function after total ischemia

Isolated guinea pig hearts were subjected to 25-min total ischemia at 37 degrees C followed by 30-min reperfusion. The product of the left ventricular isovolumic systolic pressure and heart rate representing the cardiac work index was restored to 33 +/- 5% of initial value and diastolic pressure (DP) remained substantially elevated by 47 +/- 9 mm Hg if reperfusion was resumed with initial rate 10 ml/min. The gradual restoration of perfusion rate initiating from 2 or 4 ml/min was performed in other series, and was associated with slower but higher recovery of cardiac work and lower DP by the end of reperfusion. The similar result was observed when reperfusion was resumed with initial rate but a modified solution was used for first 5 min. In which Ca++ content was reduced while K+ and Mg++ elevated. In this case final recovery of cardiac work was 59 +/- 2% and DP completely returned to initial level. It is suggested that optimal reperfusion mode should be associated with slower work recovery.     

Role of alpha- and beta-adrenoreceptors in isolated guinea pig trachea anaphylaxis to aerosol tick (D. pteronyssinus) allergy

Experiments were performed on inhalation-sensitized guinea-pigs, with the use of immunoallergic neurohistochemical techniques. Anaphylactic tracheobronchial spasm was shown to be related not only to the degree of sensitization but also to the state of alpha- and beta-adrenoreceptors. Sensitization, in its turn, changed the function of adrenoreceptors. It increased histamine sensitivity and decreased catecholamine sensitivity of an isolated organ.     

Effect of preliminary local myocardial hypoxia on the development of immune heart damage

The changes in hemo- and cardiodynamics, myocardial contractility and its structural and histochemical alterations were studied in two series of experiments (immune and combined hypoxic and immune action on the myocardium) on 27 mongrel dogs anesthesized with chloralose and urethane. It was established that preliminary short-term hypoxia of the myocardium essentially increases the alterative effect of immune factors, causing a rise in the involved area as well as in the degree of metabolic shifts in this area and in the intensity of the disorders of heart function and hemodynamics.