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ABSTRACT: The effects of densensitization of capsaicin-sensitive afferent neurons on the microcirculation in the stomach were studied
before and after administration of indomethacin at an ulcerogenic dose in adrenalectomized rats receiving and not receiving
replacement therapy with corticosterone and in sham-operated animals. Measures of the microcirculation consisted of blood
flow rates in microvessels in the submucous layer of the stomach and the diameter and permeability of microvessels in the
mucosa. Desensitization of capsaicin-sensitive afferent neurons was performed by administration of capsaicin at a dose of
100mg/kg for two weeks and adrenalectomy one week before the experiment. Blood flow rates in microvessels and microvessel
diameters were assessed in non-anesthetized rats by direct video recording methods using a special optical system with a contact
dark-field epiobjective. Administration of indomethacin at an ulcerogenic dose led to decreases in blood flow rate in microvessels
in the submucous layer, dilation of superficial microvessels in the mucosa of the stomach, and an increase in their permeability.
Desensitization of capsaicin-sensitive neurons potentiated indomethacin-induced impairments to the microcirculation in the
submucous layer and the mucosa of the stomach. These effects of densensitization were significantly enhanced in conditions
of glucocorticoid hormone deficiency. Thus, glucocorticoid hormones have favorable effects on the gastric microcirculation
in rats with desensitization of capsaicin-sensitive afferent neurons.
Neuroscience and Behavioral Physiology 04/2012; 39(6):559-564.
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ABSTRACT: One week after injection of streptozotocin (60 mg/kg intravenously), rats developed diabetes associated with a significant increase of gastric mucosa sensitivity to the ulcerogenic effect of indomethacin (35 mg/kg subcutaneously). Since potentiation of the ulcerogenic effect of indomethacin was observed only in rats subjected to fasting before drug injection, we hypothesize that this effect was caused by a drop of high glucose level in the blood after fasting.
Bulletin of Experimental Biology and Medicine 11/2011; 152(1):43-6. · 0.27 Impact Factor
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ABSTRACT: In the study, we examined the gastric mucosal susceptibility for ulcerogenic effect of indometacin at different time points of streptozotocin-induced diabetes development. Indometacin was injected at ulcerogenic dose (35 mg/kg, s. c.) on days 3, 7 and 30 after streptozotocin administration (60 mg/kg, i. v.) or its vehicle to fasted rats. Typical diabetic hyperglicaemia was observed as early as in 3 days after streptozotocin administration and accompanied with enhanced mucosal susceptibility for indometacin as compared with that of control group. In 7 and 30 days after streptozotocin administration, when hyperglicaemia was still present, the average areas of indometacin-induced erosion increased 2- and 3-fold, respectively, as compared with those observed in 3 day after streptozotocin administration. The data obtained demonstrate that gastric mucosal susceptibility for the ulcerogenic effect of indometacin is increased at the early stages of diabetes development and then aggravates along with further development of the pathological condition.
Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk 09/2011; 97(9):957-67.
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ABSTRACT: The effects of densensitization of capsaicin-sensitive afferent neurons on the microcirculation in the stomach were studied before and after administration of indomethacin at an ulcerogenic dose in adrenalectomized rats receiving and not receiving replacement therapy with corticosterone and in sham-operated animals. Measures of the microcirculation consisted of blood flow rates in microvessels in the submucous layer of the stomach and the diameter and permeability of microvessels in the mucosa. Desensitization of capsaicin-sensitive afferent neurons was performed by administration of capsaicin at a dose of 100 mg/kg for two weeks and adrenalectomy one week before the experiment. Blood flow rates in microvessels and microvessel diameters were assessed in non-anesthetized rats by direct video recording methods using a special optical system with a contact dark-field epiobjective. Administration of indomethacin at an ulcerogenic dose led to decreases in blood flow rate in microvessels in the submucous layer, dilation of superficial microvessels in the mucosa of the stomach, and an increase in their permeability. Desensitization of capsaicin-sensitive neurons potentiated indomethacin-induced impairments to the microcirculation in the submucous layer and the mucosa of the stomach. These effects of densensitization were significantly enhanced in conditions of glucocorticoid hormone deficiency. Thus, glucocorticoid hormones have favorable effects on the gastric microcirculation in rats with desensitization of capsaicin-sensitive afferent neurons.
Neuroscience and Behavioral Physiology 08/2009; 39(6):559-64.
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ABSTRACT: Prostaglandings (PGs), nitric oxide (NO) and capsaicin-sensitive afferent neurons play a pivotal role in the defensive mechanisms against gastric mucosal injury. Glucocorticoid hormones released in response to ulcerogenic stimuli are naturally occurring gastroprotective factors and exert many of the same actions in the stomach as PGs, NO and capsaicin-sensitive afferent neurons. The results reviewed suggest that glucocorticoids exert a pivotal compensatory role in the maintenance of gastric mucosal integrity in the case of impaired gastroprotective mechanisms provided by PGs, NO and capsaicin-sensitive afferent neurons. The compensatory protective action of glucocorticoids may be provided by their maintenance of glucose homeostasis and gastric microcirculation.
Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk 12/2007; 93(11):1217-28.
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ABSTRACT: The effects of desensitization of capsaicin-sensitive neurons on the blood flow velocity in microvessels of the gastric muscular membrane were investigated before and after indomethacin (35 mg/kg) administration in adrenalectomized rats with or without corticosterone replacement (4 mg/kg sc) and in sham-operated animals. Desensitization of capsaicin-sensitive neurons was performed with neurotoxic dose of capsaicin (20 + 30 + 50 mg/kg sc) two weeks before the experiment. Adrenalectomy was created one week before the experiment. The in vivo microscopy technique for direct visualization of gastric microcirculation and analysis of red blood cell (RBC) velocity was employed. Indomethacin decreased the RBC velocity. Adrenalectomy by itself profoundly decreased the RBC velocity, whereas corticosterone replacement prevented this effect. Desensitization of capsaicin-sensitive neurons did not influence the RBC velocity in sham-adrenalectomized rats; however, it induced further fall of both basal and indomethacin-induced RBC velocity in adrenalectomized rats that was prevented by corticosterone. We conclude that glucocorticoid hormones have a beneficial effect on the blood flow velocity in microvessels of the gastric muscular membrane in rats with desensitization of capsaicin-sensitive neurons.
Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk 01/2007; 92(12):1483-92.
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ABSTRACT: The results overviewed in the present article suggest that glucocorticoids released during acute activation of hypothalamic-pituitary-adrenocortical (HPA) axis are important gastroprotective factors, allowing us to re-evaluate the traditional point of view about their ulcerogenic role. It has been shown that various ulcerogenic stimuli induce an increase in glucocorticoid production that in turn helps the gastric mucosa to resist against a harmful action of ulcerogenic stimuli. Glucocorticoids released in response to mild stress contribute to adaptive gastric cytoprotection. The gastroprotective action of glucocorticoids is accounted for by maintaining the local defensive factors and inhibiting the pathogenic elements. Maintenance of glucose and temperature homeostasis as well as systemic blood pressure by glucocorticoid hormones could be a fundamental of their beneficial action on various gastric targets. Thus, glucocorticoids released during activation of HPA axis may contribute to the gastric mucosal homeostasis through their contribution to general body homeostasis.
Inflammopharmacology 01/2007; 14(5-6):207-13.
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ABSTRACT: We tested the hypothesis that contribution of glucocorticoids in gastroprotection become especially important during ablation of capsaicin-sensitive neurons. For this, the effect of desensitization of capsaicin-sensitive neurons on the gastric mucosa was compared in groups of rats with different glucocorticoid supply: sham-operated and adrenalectomized without and with corticosterone replacement (4 mg/kg sc). Functional ablation of capsaicin-sensitive neurons was performed with neurotoxic doses of capsaicin (20 + 30 + 50 mg/kg sc). Indomethacin in the dose 35 mg/kg was given as an ulcerogenic stimulus. It was shown that combination of adrenalectomy with desensitization of capsaicin-sensitive neurons potentiated the effect of sensory desensitization alone on indomethacin-induced gastric erosions. Corticosterone replacement prevented this effect of adrenalectomy. The results suggest a pivotal compensatory role of glucocorticoids in maintenance of gastric mucosal integrity during ablation of caspsaicin-sensitive sensory neurons.
Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk 09/2006; 92(8):1006-15.
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ABSTRACT: In this article we present an overview of the results of our studies suggesting that endogenous glucocorticoid hormones play a role as natural defensive factors in maintaining the integrity of the gastric mucosa during treatment with non-steroidal anti-inflammatory drugs (NSAIDs). In-domethacin and aspirin at ulcerogenic doses induce a rise in corticosterone, which helps the gastric mucosa to resist the harmful actions of these ulcerogenic agents. The gastroprotective action of glucocorticoids during NSAID treatment may be mediated by multiple actions, including maintenance of glucose homeostasis, mucus production and attenuation of enhanced gastric motility and microvascular permeability. According to our findings, glucocorticoid hormones also participate in the healing processes of NSAID-induced gastric injury. It was demonstrated that there is some cooperative interaction between glucocorticoids and prostaglandins (PGs) in gastroprotection, in a way that a deficiency of one protective factor can lead to an apparently compensatory increase of the other. The gastric mucosa becomes more susceptible to injury during deficiency of both glucocorticoids and PGs.
Inflammopharmacology 02/2005; 13(1-3):27-43.
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ABSTRACT: Our previous results demonstrate the gastroprotective but not ulcerogenic action of glucocorticoids released in response to ulcerogenic stress factors. The present study was undertaken to investigate the possible mechanisms underlying the gastroprotective action of glucocorticoids in rat stomachs. The effects of deficiency of glucocorticoid production, with or without corticosterone supplementation, on blood flow velocity in gastric microvessels, microvascular permeability, mucus production, motility as well as gastric lesions were studied 3 to 4 h after the onset of ulcerogenic stimuli: water-restraint stress or indomethacin administration. The contribution of glucocorticoids in the healing process of gastric injury was also evaluated. The deficiency in glucocorticoid production significantly potentiated the functional disorders induced by ulcerogenic stimuli, such as a decrease in blood flow velocity and mucus production and an increase in gastric motility and in microvascular permeability, which resulted in aggravation of the formation of gastric lesions as well as impairment of their healing. The changes observed were prevented by supplementation of corticosterone at a dose mimicking a stress-induced corticosterone rise. We conclude that a gastroprotective action of glucocorticoids may be provided by multiple actions, including maintenance of the gastric mucosal blood flow and mucus production, attenuation of the enhanced gastric motility and microvascular permeability as well as beneficial influences on healing processes.
Annals of the New York Academy of Sciences 07/2004; 1018:288-92. · 3.15 Impact Factor
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ABSTRACT: We studied the effects of adrenalectomy and replacement therapy on healing of gastric erosions in adult Sprague-Dawley rats developed 4 h after subcutaneous injection of indomethacin in a dose of 25 or 35 mg/kg. Adrenalectomy was performed 1 week before or 4 h after indomethacin administration. Healing was evaluated by changes in the area of erosions over 24 h after indomethacin administration at fixed time intervals. Plasma corticosterone was measured. Adrenalectomy (irrespective of the time of intervention) decelerated healing of gastric injuries. Injection of corticosterone in a physiological dose of 4 mg/kg at the initial stage of healing (4 h after indomethacin administration) improved healing of erosions.
Bulletin of Experimental Biology and Medicine 12/2003; 136(5):435-7. · 0.27 Impact Factor
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ABSTRACT: Effects of glucocorticoid deficiency followed by corticosterone replacement on the healing of gastric erosions and chronic gastric ulcers have been investigated in rats. Glucocorticoid deficiency was induced by adrenalectomy performed after the formation of gastric erosions or ulcers. Gastric erosions were produced by indomethacin (35 mg/kg, i.p.) or by 6 h immobilization at temperature 8 degrees C, chronic gastric ulcers were induced by 60% acetic acid. All ulcerogenic stimuli caused an increase in corticosterone production. Adrenalectomy created corticosterone deficiency and delayed the healing of gastric erosions and chronic gastric ulcers. The effect of adrenalectomy was more evident in the indomethacin ulcerogenic model. Replacement by corticosterone prompted the healing of gastric erosions and ulcers in adrenalectomized animals. These data suggest a participation of endogenous glucocorticoids in a restoration of gastric mucosal integrity.
Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk 10/2003; 89(9):1137-46.
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ABSTRACT: Effects of glucocorticoid deficiency and corticosterone replacement on gastric mucosal injury induced by various ulcerogenic stimuli have been evaluated in rats. Gastric erosions were induced in male rats by stimuli of different modalities and intensities. Glucocorticoid deficiency was induced by adrenalectomy or delayed inhibitory action after a single pharmacological dose of cortisol (300 mg/kg, i.p.) injected one week before the onset of ulcerogenic stimulus. Ulcerogenic stimuli induced both a plasma corticosterone rise and a gastric mucosal injury. The area of mucosal damages induced various stimuli ranging from a small to extensive those. Glucocorticoid deficiency significantly potentiated an ulcerogenic action of each ulcerogenic stimulus. Replacement by corticosterone (4 mg/kg, s.c., 15 min before the onset of ulcerogenic stimulus) prevented or significantly decreased the erosion--potentiating effect of glucocorticoid deficiency. These results show that endogenous glucocorticoids released during ulcerogenic influences help gastric mucous membrane to resist against a harmful action of both weak and strong ulcerogenic stimuli.
Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk 06/2002; 88(5):602-11.
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ABSTRACT: Pretreatment with a single large dose of cortisol a week before indomethacin administration, or an adrenalectomy induced a glucocorticoid production deficiency in rats. The area of gastric erosions in these rats was considerably larger than in the control animals in 4, 24, and 48 hours after the indomethacin administration. Administration of corticosterone noticeably prompted the healing of the erosions in the rats with glucocorticoid deficiency. The findings suggest a gastroprotective effect of glucocorticoids in healing of indomethacin-induced mucosal injury.
Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk 07/2000; 86(6):720-7.
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T T Podvigina
Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk 04/1999; 85(3):462-5.
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ABSTRACT: The corticosterone concentrations were determined in the blood of unrestrained rats exposed to 7 successive trials with 30-min. intervals. This study revealed that hormonal responses of the pituitary-adrenocortical system to stress were decreased, whereas the time of the system recovery was reduced after re-exposure to electric shock. The change seems to be dependent on the strength of the stress agent and the number of re-exposures.
Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk 01/1999; 84(12):1386-93.
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ABSTRACT: Circadian responses of the hypophyseal-adrenal axis to stress were greater is the PM as compared with AM after small stress intensity, but it were similar after high stress intensity. Was shown to depend on the intensity of the stress factor. The circadian variations of the adrenal glands response to the ACTH seem to play a major role in determining the character of the hypophyseal-adrenal axis response to stress.
Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk 05/1997; 83(4):59-66.
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ABSTRACT: Hypothalamo-pituitary-adrenocortical axis reactivity was studied in vivo and in vitro in 7 days after single administration of 30 mg/100 g body weight of hydrocortisone in rats. There were a blockade of stress-induced decrease of CRF-41 content in median eminence, and failure of increase of ACTH and corticosterone levels in the blood to stress in 7 days after hydrocortisone administration. A decrease of reactivity to ACTH was shown during incubation of adrenals from rats treated with hydrocortisone. 300 and 400 mg/100 g body weight of corticosterone s. c. imitates a stress-induced increase of corticosterone in the blood and can be used as replacement therapy. We conclude that high supraphysiological doses of glucocorticoids results in a decrease of reaction of hypothalamus, pituitary and adrenals to stress.
Fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk 02/1995; 81(1):24-31.
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ABSTRACT: The circadian relationships between blood corticosteroids and latent period of pain reaction to hot stimulation were investigated in man and rats. There were no correlation of blood corticosteroids levels and pain latent period but the latent period increased during those time of day when the corticosteroids levels were higher in total: man--morning and day, rats--evening and night.
Fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk 10/1993; 79(9):81-8.
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ABSTRACT: The effect of stress on adrenal response to ACTH was studied in vivo and in vitro in rats. There were a decrease of capacity and an increase of responsiveness to ACTH of adrenals from rats which were exposed to electrical stimulation of foot. The date explain the mechanisms of hypothalamo-pituitary-adrenocortical system changes in total after stress which was obtained in our previous work.
Fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk 01/1993; 78(12):149-54.
