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
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
The aim of the present study was to evaluate the effect of short-term adrenergic blockade on the rate of whole-body protein turnover and leucine oxidation, and on protein synthesis in specific tissues in male rats. Adrenergic blockade was induced by guanethidine (100 mg/kg body weight subcutaneously). The control group was treated with saline. On the second day, the parameters of whole-body protein and leucine metabolism were evaluated using a primed constant intravenous infusion of L-[1-(14)C]leucine. Protein synthesis in tissues was determined on the basis of L-[1-(14)C]leucine incorporation. Guanethidine treatment caused a decrease in norepinephrine in skeletal muscle. Whole-body leucine oxidation and leucine oxidized fraction were higher in guanethidine-treated rats. There was an insignificant effect of guanethidine on whole-body proteolysis, protein synthesis and leucine clearance. However, protein balance was negative due to the larger difference between protein synthesis and proteolysis in guanethidine-treated animals compared to controls. In guanethidine-treated rats, protein synthesis was higher in the gastrocnemius muscle and in the kidneys and lower in liver and spleen. Changes in the small intestine and colon were insignificant. In addition, a marked decrease in concentration of several amino acids has been observed in the liver, the kidneys and the spleen. It is concluded that adrenergic blockade induced by guanethidine is associated with significant changes in protein metabolism, leucine oxidation and amino acid concentrations in several tissues. The most important consequences of treatment are considered to be a negative effect on protein balance, increased protein turnover in skeletal muscle and kidneys and decreased protein synthesis in the liver and spleen. These changes may also be induced by administration of other sympathetic blocking agents, e.g. in treatment of hypertension.
- MeSH
- adrenergní látky farmakologie MeSH
- aminokyseliny analýza MeSH
- guanethidin farmakologie MeSH
- játra účinky léků metabolismus MeSH
- jejunum účinky léků metabolismus MeSH
- kolon účinky léků metabolismus MeSH
- kosterní svaly účinky léků metabolismus MeSH
- krysa rodu Rattus MeSH
- ledviny účinky léků metabolismus MeSH
- leucin metabolismus MeSH
- noradrenalin analýza MeSH
- oxidace-redukce MeSH
- potkani Wistar MeSH
- proteiny metabolismus MeSH
- slezina účinky léků metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adrenergní látky MeSH
- aminokyseliny MeSH
- guanethidin MeSH
- leucin MeSH
- noradrenalin MeSH
- proteiny MeSH
Vasoactive intestinal polypeptide (VIP) is believed to coexist with acetylcholine in postganglionic parasympathetic neurones. However, the presence of VIP in extrinsic nerves and/or other types of intrinsic cardiac neurones has not been excluded. The aim of our study was to examine the distribution and origin of VIP-ergic innervation in the rat heart atria using immunocytochemistry and radioimmunoassay (RIA) combined with two types of denervation: sympathectomy, which was produced by guanethidine treatment and sensory denervation achieved by capsaicin administration. In whole-mount preparations of the intact atria, VIP-immunoreactive (IR) nerve fibres and ganglionic cells were found, the latter being much more numerous in the left atria (LA) than in the right ones. Some of VIP-IR nerve fibres forming bundles appeared to be extrinsic in origin. VIP-IR concentrations determined by RIA in the intact rats were significantly higher in the LA than in the right ones (p < 0.01). However, no changes in VIP-IR levels were found in either atrium after both guanethidine and capsaicin treatment protocols, thus indicating that VIP-immunoreactivity is not associated with either sympathetic or sensory innervation. In conclusion, the ganglionated plexus of the rat atria may comprise at least 3 different neuronal populations expressing VIP-positivity: 1. extrinsic preganglionic parasympathetic fibres, 2. intrinsic postganglionic parasympathetic neurones and 3. intrinsic local circuit neurones that do not express a cholinergic phenotype.
- MeSH
- cholin-O-acetyltransferasa metabolismus MeSH
- ganglia autonomní cytologie metabolismus MeSH
- guanethidin farmakologie MeSH
- imunohistochemie MeSH
- kapsaicin farmakologie MeSH
- krysa rodu Rattus MeSH
- myokard cytologie metabolismus MeSH
- nervová vlákna metabolismus ultrastruktura MeSH
- srdce účinky léků MeSH
- srdeční síně inervace MeSH
- thiolesterasa ubikvitinu MeSH
- thiolesterhydrolasy analýza MeSH
- vazoaktivní intestinální peptid metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cholin-O-acetyltransferasa MeSH
- guanethidin MeSH
- kapsaicin MeSH
- thiolesterasa ubikvitinu MeSH
- thiolesterhydrolasy MeSH
- vazoaktivní intestinální peptid MeSH
The relationship between neurogenic responses of longitudinal and circular muscle was studied by measuring contractions and EMG or nonadrenergic, non-cholinergic (NANC) relaxations and NANC inhibitory junction potentials in different preparations of the guinea-pig ileum. NANC relaxation of longitudinal muscle was observed also without any preceding or concomitant circular muscle contraction ruling out the possibility that the latter might be the cause of the NANC relaxation. Circular muscle twitches or powerful contractions were absent if there was no preceding neurogenic or myogenic excitation of longitudinal muscle; in preparations with myenteric plexus-longitudinal muscle layers removed only small residual responses were seen although still under neurogenic influences. Thus excitation of longitudinal muscle seemed a prerequisite for synchronized and powerful contractions of circular muscle to occur. Cholinergic contraction and NANC relaxation of longitudinal muscle evoked by field stimulation were partly inhibited if the submucous plexus was also present suggesting the involvement of a more complex neuronal circuitry in these responses.
- MeSH
- adenosintrifosfát farmakologie MeSH
- atropin farmakologie MeSH
- elektrická stimulace MeSH
- elektromyografie MeSH
- evokované potenciály účinky léků MeSH
- guanethidin farmakologie MeSH
- histamin farmakologie MeSH
- hladké svalstvo účinky léků inervace fyziologie MeSH
- ileum účinky léků inervace fyziologie MeSH
- mikroelektrody MeSH
- morčata MeSH
- peristaltika MeSH
- plexus myentericus fyziologie MeSH
- svalová kontrakce MeSH
- techniky in vitro MeSH
- tetrodotoxin farmakologie MeSH
- zvířata MeSH
- Check Tag
- morčata MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- adenosintrifosfát MeSH
- atropin MeSH
- guanethidin MeSH
- histamin MeSH
- tetrodotoxin MeSH
The effect of various autonomic blockers on the heart rate (from the ECG recording) of intact rats and of animals with experimental hyperthyroidism induced by the administration of dried thyroid was studied. In intact rats, the heart rate fell significantly (by 22%) during the first week after the peroral administration of propranolol (0.05% in food), but trimepranol (0.02%), reserpine (0.001%) and guanethidine (0.1%) had no effect (in a suplementary experment, a small, but statistically significant decrease was also found after trimepranol). In experimental hyperthyroidism, using the same blocker doses, the heart rate fell significantly after propranolol (by 23%), trimepranol (22%), reserpine (16%) and, in a preliminary experiment, guanethidine (19%). On injecting 0.05 mg propranolol intravenously, the maximum drop in the heart rate in intact rats was 22%, while in hyperthyroidism it was hardly more than half this value (at all the intervals from 2 to 30 minutes the decrease was statistically significant). Practolol, in a dose of 0.3 mg i.v., was less effective -- in intact rats the heart rate fell by not more than 12% (at all the intervals from 2 to 30 minutes the decrease was significant), but in hyperthyroidism the drop was slower and statistically non-significant. The results do not furnish an unequivocal answer to the question of the role of adrenergic regulation of the heart rate under physiological conditions and in experimental hyperthyroidism in rats.
- MeSH
- guanethidin farmakologie MeSH
- hypertyreóza patofyziologie MeSH
- krysa rodu Rattus MeSH
- praktolol farmakologie MeSH
- propranolol farmakologie MeSH
- reserpin farmakologie MeSH
- srdeční frekvence účinky léků MeSH
- sympatolytika farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- guanethidin MeSH
- praktolol MeSH
- propranolol MeSH
- reserpin MeSH
- sympatolytika MeSH
- MeSH
- cévní rezistence MeSH
- funkční vyšetření srdce MeSH
- guanethidin farmakologie MeSH
- hematokrit MeSH
- hemodynamika * MeSH
- hodnoty glomerulární filtrace MeSH
- hypertenze patofyziologie MeSH
- krevní objem MeSH
- krevní tlak MeSH
- ledviny krevní zásobení patofyziologie MeSH
- lidé MeSH
- methyldopa farmakologie MeSH
- minutový srdeční výdej MeSH
- postura těla MeSH
- regionální krevní průtok MeSH
- srdeční frekvence MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- guanethidin MeSH
- methyldopa MeSH
- MeSH
- abnormální reflex MeSH
- apnoe patofyziologie MeSH
- arterie MeSH
- chemická stimulace MeSH
- dýchací soustava účinky léků MeSH
- dýchání účinky léků MeSH
- fenoxybenzamin farmakologie MeSH
- glottis účinky léků MeSH
- guanethidin farmakologie MeSH
- hydrogenované námelové alkaloidy farmakologie MeSH
- kardiovaskulární systém účinky léků MeSH
- králíci MeSH
- krevní tlak účinky léků MeSH
- nosní sliznice patofyziologie MeSH
- srdeční frekvence účinky léků MeSH
- sympatolytika farmakologie MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fenoxybenzamin MeSH
- guanethidin MeSH
- hydrogenované námelové alkaloidy MeSH
- sympatolytika MeSH
- MeSH
- adrenalin farmakologie terapeutické užití MeSH
- epitel účinky léků MeSH
- glaukom farmakoterapie MeSH
- guanethidin farmakologie terapeutické užití MeSH
- karbachol farmakologie terapeutické užití MeSH
- králíci MeSH
- kultivační techniky MeSH
- lidé MeSH
- neostigmin farmakologie terapeutické užití MeSH
- oční roztoky MeSH
- pilokarpin farmakologie terapeutické užití MeSH
- psi MeSH
- rohovka účinky léků MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- lidé MeSH
- psi MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- adrenalin MeSH
- guanethidin MeSH
- karbachol MeSH
- neostigmin MeSH
- oční roztoky MeSH
- pilokarpin MeSH
- MeSH
- antihypertenziva farmakologie MeSH
- bretyliové sloučeniny farmakologie MeSH
- guanethidin farmakologie MeSH
- kolaterální oběh účinky léků MeSH
- koronární cévy * MeSH
- psi MeSH
- regionální krevní průtok účinky léků MeSH
- srdeční frekvence účinky léků MeSH
- sympatolytika farmakologie MeSH
- zvířata MeSH
- Check Tag
- psi MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antihypertenziva MeSH
- bretyliové sloučeniny MeSH
- guanethidin MeSH
- sympatolytika MeSH
