The effect of chemical sympathectomy on cardiovascular parameters and the compensatory role of adrenal hormones, the renin-angiotensin system, and cardiovascular sensitivity to vasoconstrictors were studied in spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats. Sympathectomy was induced in 20-week-old rats by daily intraperitoneal guanethidine administration (30 mg/kg b.w.) for 2 weeks. Basal blood pressure (BP), heart rate (HR), and restraint stress-induced cardiovascular changes were measured by radiotelemetry. The BP response to catecholamines was determined in rats with implanted catheters. Sympathectomy decreased BP only transiently, and after 14-day guanethidine treatment, BP returned to basal values in both strains. Sympathectomy permanently lowered HR, improved baroreflex sensitivity, and decreased the low-frequency domain of systolic blood pressure variability (a marker of vascular sympathetic activity). Guanethidine also attenuated the BP and HR responses to restraint stress. On the other hand, the BP response to catecholamines was augmented in sympathectomized rats, and this was not due to the de novo synthesis of vascular adrenergic receptors. Sympathectomy caused adrenal enlargement, enhanced the expression of adrenal catecholamine biosynthetic enzymes, and elevated plasma adrenaline levels in both strains, especially in WKY rats. Guanethidine also increased the plasma levels of aldosterone and corticosterone in WKY rats only. In conclusion, sympathectomy produced a transient decrease in BP, a chronic decrease in HR and improvement in baroreflex sensitivity. The effect of sympathectomy on BP was counteracted by increased vascular sensitivity to catecholamines in WKY rats and SHRs and/or by the enhanced secretion of adrenal hormones, which was more pronounced in WKY rats.
- Klíčová slova
- Adrenal medulla, Blood pressure response, Catecholamines, Guanethidine, Vascular wall innervation,
- MeSH
- baroreflex účinky léků MeSH
- cévy účinky léků inervace patofyziologie MeSH
- fyzické omezení MeSH
- guanethidin farmakologie MeSH
- hypertenze patofyziologie MeSH
- kardiovaskulární fyziologické jevy účinky léků MeSH
- katecholaminy metabolismus MeSH
- krevní tlak účinky léků MeSH
- krysa rodu Rattus MeSH
- nadledviny růst a vývoj metabolismus patofyziologie MeSH
- potkani inbrední SHR MeSH
- potkani inbrední WKY MeSH
- psychický stres MeSH
- srdeční frekvence účinky léků MeSH
- sympatolytika farmakologie MeSH
- vazokonstriktory farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- guanethidin MeSH
- katecholaminy MeSH
- sympatolytika MeSH
- vazokonstriktory MeSH
Parkinson's disease (PD) is a neurodegenerative disease with a progressive loss of mesencephalic dopaminergic neurons of the substantia nigra (SN). To further evaluate its pathophysiology, accurate animal models are needed. The current study aims to verify the impact of a 6-hydroxydopamine (6-OHDA) bilateral microinjection into the SN on gastrointestinal symptoms in rats and confirm that the 6-OHDA rat model is an appropriate tool to investigate the mechanisms of Parkinsonian GI disorders. Immunohistochemistry, digital X-ray imaging, short-circuit current, FITC-dextran permeability and ultra-performance liquid chromatography tandem mass spectrometry were used in this study. The results indicated that the dopaminergic neurons in SN and fibres in the striatum were markedly reduced in 6-OHDA rats. The 6-OHDA rats manifested reductions in occupancy in a rotarod test and increases in daily food debris but no difference in body mass or daily consumption. Compared with control rats, faecal pellets and their contents were significantly decreased, whereas gastric emptying and intestinal transport were delayed in 6-OHDA rats. The increased in vivo FITC-dextran permeability and decreased intestinal transepithelial resistance in the model suggest attenuated barrier function in the digestive tract in the PD model. Moreover, inflammatory factors in the plasma showed that pro-inflammatory factors IL-1? and IL-8 were significantly increased in 6-OHDA rats. Collectively, these findings indicate that the model is an interesting experimental tool to investigate the mechanisms involved in the progression of gastrointestinal dysfunction in PD.
- MeSH
- gastrointestinální nemoci chemicky indukované diagnostické zobrazování patofyziologie MeSH
- krysa rodu Rattus MeSH
- oxidopamin toxicita MeSH
- parkinsonské poruchy chemicky indukované diagnostické zobrazování patofyziologie MeSH
- potkani Sprague-Dawley MeSH
- sympatolytika toxicita MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- oxidopamin MeSH
- sympatolytika MeSH
Breathing impairments, such as an alteration in breathing pattern, dyspnoea, and sleep apnoea, are common health deficits recognised in Parkinson's disease (PD). The mechanism that underlies these disturbances, however, remains unclear. We investigated the effect of the unilateral damage to the rat nigrostriatal pathway on the central ventilatory response to hypercapnia, evoked by administering 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle (MFB). The respiratory experiments were carried out in conscious animals in the plethysmography chamber. The ventilatory parameters were studied in normocapnic and hyperoxic hypercapnia before and 14 days after the neurotoxin injection. Lesion with the 6-OHDA produced an increased tidal volume during normoxia. The magnified response of tidal volume and a decrease of breathing frequency to hypercapnia were observed in comparison to the pre-lesion and sham controls. Changes in both respiratory parameters resulted in an increase of minute ventilation of the response to CO(2) by 28% in comparison to the pre-lesion state at 60 s. Our results demonstrate that rats with implemented unilateral PD model presented an altered respiratory pattern most often during a ventilatory response to hypercapnia. Preserved noradrenaline and specific changes in dopamine and serotonin characteristic for this model could be responsible for the pattern of breathing observed during hypercapnia.
- MeSH
- fasciculus telencephali medialis účinky léků fyziologie MeSH
- hyperkapnie patofyziologie MeSH
- krysa rodu Rattus MeSH
- oxidopamin toxicita MeSH
- parkinsonské poruchy chemicky indukované patofyziologie MeSH
- plicní ventilace účinky léků fyziologie MeSH
- potkani Wistar MeSH
- sympatolytika toxicita MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- oxidopamin MeSH
- sympatolytika MeSH
Existing experimental studies of the effect of sympathetic nerve fibers on bone marrow cells are based on the systemic administration of neurotoxic 6-hydroxydopamine. The method of global chemical sympathectomy has some serious disadvantages and could lead to questionable results. We describe a new method of local chemical sympathectomy of rat femoral bone marrow using guanethidine (Ismelin) delivery using an osmotic mini pump. Local guanethidine treatment for 14days led to complete elimination of sympathetic fibers in femoral bone marrow in contrast to bone marrow of contralateral or naïve femurs. Ablation of sympathetic fibers was associated with a loss of rat endothelial cell marker (RECA) indicating immunophenotype changes in blood vessel endothelial cells, but no significant effect of guanethidine was found on the survival of endothelial cells and mesenchymal stem cells in vitro. Moreover, local guanethidine treatment also elicited a significant reduction of Nestin+/SDF1+ mesenchymal stem cells and c-Kit+/CD90+ hematopoietic stem cells in femoral bone marrow. Tissue-specific chemical sympathectomy of rat bone marrow by guanethidine overcomes some of the drawbacks of systemic administration of neurotoxic compounds like 6-hydroxydopamine and delivers unequivocal evidence on the effects of sympathetic innervation on the cell content of bone marrow.
- Klíčová slova
- Endothelial cells, Guanethidine, Osmotic mini pump, Sympathetic innervation,
- MeSH
- endoteliální buňky pupečníkové žíly (lidské) účinky léků metabolismus patologie MeSH
- femur účinky léků inervace metabolismus patologie MeSH
- fluorescenční protilátková technika MeSH
- guanethidin farmakologie MeSH
- kostní dřeň účinky léků inervace metabolismus MeSH
- lidé MeSH
- mezenchymální kmenové buňky účinky léků metabolismus patologie MeSH
- modely u zvířat MeSH
- potkani Wistar MeSH
- průtoková cytometrie MeSH
- sympatektomie chemická MeSH
- sympatický nervový systém účinky léků metabolismus patologie MeSH
- sympatolytika farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- guanethidin MeSH
- sympatolytika MeSH
To evaluate the sympathetic innervation of the female diabetic heart, resting heart rate and sympathetic tone were assessed in vivo, and effect of tyramine on spontaneous beating rate, norepinephrine atrial concentrations, uptake, and release were determined in vitro in streptozotocin- (STZ-) treated rats and respective controls aged 3 months to 2 years. Resting bradycardia, decreased sympathetic tone, deceleration of spontaneous beating rate, and slightly declining carrier-mediated, but preserved exocytotic norepinephrine release from the atria were found in younger diabetic rats while the reactivity of the right atria to tyramine was not affected with age and disease duration. Diabetic two-year-old animals displayed symptoms of partial spontaneous recovery including normoglycemia, increased plasma insulin concentrations, fully recovered sympathetic tone, but putative change, in releasable norepinephrine tissue stores. Our data suggested that female diabetic heart exposed to long-lasting diabetic conditions seems to be more resistant to alteration in sympathetic innervation than the male one.
- MeSH
- atropin farmakologie MeSH
- časové faktory MeSH
- experimentální diabetes mellitus chemicky indukované metabolismus patofyziologie MeSH
- inzulin metabolismus MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- metipranolol farmakologie MeSH
- pohlavní dimorfismus MeSH
- potkani Wistar MeSH
- srdce účinky léků inervace patofyziologie MeSH
- srdeční frekvence účinky léků fyziologie MeSH
- streptozocin MeSH
- sympatický nervový systém účinky léků patologie patofyziologie MeSH
- sympatolytika farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- atropin MeSH
- inzulin MeSH
- metipranolol MeSH
- streptozocin MeSH
- sympatolytika MeSH
The study was carried out in a population of 139 men, divided into two control groups: 40 non-smokers and 39 smokers not exposed to chemical compounds, and two groups exposed to them: 19 non-smokers and 41 cigarette smokers with occupational contact with organic solvents. The results of toxicological analyses of air and chromatographic analyses of solvents demonstrated the presence of benzene, toluene, xylene and their partly hydrogenated derivatives, paraffin hydrocarbons, oleins, naphthenes (components of painter's naphtha), monohydric and polyhydric alcohols (butanol, cyclohexanol, butylene glycol) esters (ethyleneglycol acetate, butyl acetate) and ketones (methylisobutyl ketone, cyclohexanone). In the time of the studies the TWA values for benzene were 0 to 38 mg x m-3 (0 to 12 ppm), with arithmetic mean averages of about 19 mg x m-3 (6 ppm) and for the level of benzene 0-351 mg x m-3 (0-110 ppm) with arithmetic mean annual averages of about 48 mg x m-3 (15 ppm). Mean phenol concentration in the urine of the workers in groups I, II, III and IV respectively was: 7.9 +/- 3.5; 10.0 +/- 5.8; 16.8 +/- 6.2 and 18.4 +/- 9.7 mg x l-1. Hippuric acid concentration in the urine of the workers in groups I to IV was: 496 +/- 326, 538 +/- 341, 982 +/- 420 and 1107 +/- 507 mg x l-1 respectively. The absolute counts were determined of T-cells (CD 3+), T-helper (CD 4+), T-suppressor (CD 8+) cells and natural killer (NK) cells (CD 16+) in the peripheral blood by indirect immunofluorescence. In the subjects with occupational exposure to organic solvents the counts of T-cells and NK-cells were reduced, and the number of T-suppressor cells was raised which resulted in a decrease of the T-helper/T-suppressor ratio. These changes were more pronounced in cigarette smokers. The assessment of the immunotoxic effect of organic solvents during occupational exposure should take into consideration the possibility of a synergistic action with tobacco and may be of practical use for monitoring the toxic effect of organic solvents on the lymphocyte system.
- MeSH
- buňky NK účinky léků metabolismus MeSH
- dospělí MeSH
- fenol MeSH
- fenoly moč MeSH
- kouření škodlivé účinky MeSH
- látky znečišťující vzduch v pracovním prostředí analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- počet lymfocytů MeSH
- pracovní expozice * MeSH
- rozpouštědla škodlivé účinky analýza MeSH
- sympatolytika moč MeSH
- synergismus léků MeSH
- T-lymfocyty účinky léků metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky kontrolované MeSH
- klinické zkoušky MeSH
- Názvy látek
- fenol MeSH
- fenoly MeSH
- látky znečišťující vzduch v pracovním prostředí MeSH
- rozpouštědla MeSH
- sympatolytika MeSH
Previous morphological and physiological studies have suggested that the adrenergic innervation of the dorsal motor nucleus of the vagus nerve (dmnX) is involved in direct synaptic inhibition of parasympathetic preganglionic neurones of the vagus that control secretion of pancreatic insulin. We investigated the effects of bilateral 6-hydroxydopamine (6-OHDA) lesions of adrenergic innervation of the dmnX on pancreatic insulin secretion and glycaemia in normal and vagotomized rats. After two weeks the 6-OHDA lesions produced a marked increase in circulating insulin levels, but no change in glycaemia. Hyperinsulinaemia after adrenergic denervation of the dmnX was more pronounced when a glucose bolus was injected intraarterially. Bilateral subdiaphragmatic vagotomy reversed the observed hyperinsulinaemia. This targeted pharmacological lesion of the adrenergic innervation of dmnX thus causes hypersecretion by pancreatic B cells, an effect which requires an intact vagus nerve.
- MeSH
- glukosa farmakologie MeSH
- inzulin krev metabolismus MeSH
- krevní glukóza analýza MeSH
- krysa rodu Rattus MeSH
- Langerhansovy ostrůvky metabolismus MeSH
- medulla oblongata fyziologie MeSH
- nervus vagus fyziologie MeSH
- oxidopamin farmakologie MeSH
- potkani Sprague-Dawley MeSH
- sekrece inzulinu MeSH
- sympatektomie chemická MeSH
- sympatolytika farmakologie MeSH
- vagotomie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- glukosa MeSH
- inzulin MeSH
- krevní glukóza MeSH
- oxidopamin MeSH
- sympatolytika MeSH
It is now generally accepted, that in most of the animal species the adrenergic control of lipolysis from adipose tissue is mediated by adrenergic beta 1 and alpha 2 receptors. Therefore, the problem we deal with in this article is concerned with the role of alpha adrenergic receptors in lipolysis in the rat adipose tissue because only in this species the function of alpha adrenergic receptors in lipolysis is still not clear. In in vitro experiments with epididymal adipose tissue of adult rats (where we followed up the release of free fatty acids into the albumin medium) we found: 1) Alpha adrenergic blocking agents phentolamine and phenoxybenzamine had no influence on the lipid mobilizing effect of adrenergic agonists. This effect was absent also when drugs with the strong alpha sympathomimetic effects, e.g. norepinephrine and noroxedrine, were used. 2) On the other hand, alpha adrenergic agonist phenylephrine was able to antagonize in rat adipose tissue the lipid mobilizing effect of beta adrenergic agonist isoproterenol. 3) From our experiments it can be concluded, that phenylephrine acts as a competitive dualist on beta adrenergic receptors, it reduces the effect of full agonist (e.g. isoproterenol) to the level of its own maximum lipolytic effect. No participation of alpha adrenergic receptors in described effects of phenylephrine were detected, because neither the lipolytic, nor the lipolysis blocking effects of phenylephrine were influenced by alpha adrenergic blocking agents. Our studies using alpha adrenergic agonist phenylephrine or nonselective alpha adrenergic blocking agents did not indicate the presence of any alpha adrenergically controlled lipolysis in the rat adipose tissue. However, the role of antilipolytic alpha 2 adrenoceptors in rat adipose tissue cannot be completely excluded, some of these receptors were found on the membranes of rat adipocytes. Our future study deals with this problem.
- MeSH
- agonisté adrenergních beta-receptorů farmakologie MeSH
- alfa blokátory farmakologie MeSH
- inbrední kmeny potkanů MeSH
- krysa rodu Rattus MeSH
- lipolýza účinky léků MeSH
- sympatolytika farmakologie MeSH
- sympatomimetika farmakologie MeSH
- techniky in vitro MeSH
- tuková tkáň metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- agonisté adrenergních beta-receptorů MeSH
- alfa blokátory MeSH
- sympatolytika MeSH
- sympatomimetika MeSH
Xylazine (rompun) has sedative, analgetic and myorelaxative effects; in addition to this, it also influences the homeostasis of glucose in the organism. The changes in glucose tolerance were studied in young rats after the administration of xylazine in combination with the blockers of adrenergic receptors. Xylazine caused hyperglycaemia and glucose intolerance in young rats and the administration of the beta-adrenergic blocker (propranolol) prolonged this diabetogenic effect. On the other hand, glucose tolerance after the administration of xylazine with alpha-adrenergic blocker (phentolamine) is close to the normal level. It is supposed on the basis of our results that xylazine-induced glucose intolerance and hyperglycaemia are mediated by the stimulation of the alpha-adrenergic system. Besides inhibition of insulin secretion, hepatic glycogenolysis probably also increases.
- MeSH
- glukózový toleranční test * MeSH
- inbrední kmeny potkanů MeSH
- krevní glukóza analýza MeSH
- krysa rodu Rattus MeSH
- sympatolytika farmakologie MeSH
- thiaziny farmakologie MeSH
- xylazin farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- krevní glukóza MeSH
- sympatolytika MeSH
- thiaziny MeSH
- xylazin MeSH
- MeSH
- atropin farmakologie MeSH
- cystamin toxicita MeSH
- efedrin farmakologie MeSH
- inbrední kmeny potkanů MeSH
- krysa rodu Rattus MeSH
- sympatolytika farmakologie MeSH
- sympatomimetika farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- atropin MeSH
- cystamin MeSH
- efedrin MeSH
- sympatolytika MeSH
- sympatomimetika MeSH