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  • 1
    ISSN: 1474-8673
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 1 It was shown recently that stimulation of cardiac muscarinic M2-receptors revealed an enhanced negative inotropic response in isolated rat left atria after exposure to hypochlorite-induced oxidative stress. This phenomenon was not observed after stimulation of the cardiac A1-receptor, which like the M2-receptor is coupled to Gi-proteins. Since even the contractile response to M3-receptor stimulation was not amplified in the rat portal vein, we hypothesized a M2-receptor specificity of this hypochlorite-induced enhancement. 2 The present study was performed in order to investigate whether the sympathoinhibitory response to presynaptically located M2-receptor stimulation would also be modified after exposure to hypochlorite in the rat tail artery. We applied electrical field stimulation (EFS) in order to mimic sympathetic neurotransmission. 3 EFS increased the vascular tone frequency-dependently (0.3–4 Hz). EFS-induced vasoconstriction could be attenuated by acetylcholine (30 nm−1 μm) in a concentration-dependent manner. Hypochlorite (10 and 100 μm) did not affect the sympathoinhibitory effect of acetylcholine (100 nm). 4 In conclusion, in contrast to cardiac M2-receptors, hypochlorite did not amplify the sympathoinhibitory effects of presynaptic M2-receptors. The different responsiveness between neuronal and cardiac M2-receptors to hypochlorite may be explained by the different G-protein subunits involved in the activation of the underlying signalling cascade.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Autonomic & autacoid pharmacology 23 (2003), S. 0 
    ISSN: 1474-8673
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 1 The present study was designed to analyse the possible involvement of V1- and V2-receptors in vasopressin (AVP)-induced facilitation of the sympathetic nervous system. Furthermore, we aimed to determine whether the site of facilitation by AVP is located pre- or postsynaptically. 2 Electrical field stimulation (EFS) was applied on the rat mesteric artery to activate the sympathetic nervous system. In addition, we evaluated the direct vascular effects of AVP. The postsynaptic effect of AVP on the sympathetic nervous system was investigated by exposing the vessels to exogenous noradrenaline. These experiments were performed in the absence or presence of selective V1 and V2 receptor antagonists SR 49059 and SR 121463, respectively. Desmopressin was applied as a selective V2 agonist. 3 The direct vasoconstrictor effect of AVP was antagonized by SR 49059 and not by SR 121463. Desmopressin neither showed any direct vasoconstrictor effect nor produced vasodilatation after a precontraction induced by noradrenaline (10 μm). The EFS-induced rise in vascular tone could be increased by a sub-pressor concentration of AVP. This fascilitation could be antagonized by SR 49059, but not by SR 121463. Desmopressin did not influence the increase in vascular tone during EFS. Vasoconstriction induced by exogenous noradrenaline could be facilitated by a sub-pressor concentration of AVP and this selective postsynaptic effect could be antagonized by V1-receptor blockade. 4 In conclusion, the AVP-induced facilitation of the sympathetic nervous system is completely V1-receptor dependent and at least partly postsynaptically mediated.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Autonomic & autacoid pharmacology 23 (2003), S. 0 
    ISSN: 1474-8673
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 1 The present survey is dealing with the interactions between the renin–angiotensin–aldosterone system (RAAS) and the sympathetic nervous system (SNS) in various organs and tissues, with an emphasis on the angiotensin AT-receptors located at the sympathetic nerve endings. 2 Angiotensin II, the main effector of the RAAS is known to stimulate sympathetic nerve traffic and its sequelae in numerous organs and tissues, such as the central nervous system, the adrenal medulla, the sympathetic ganglia and the sympathetic nerve endings. These stimulatory effects are mediated by AT1-receptors and counteracted by AT1-receptor antagonists. 3 Sympatho-inhibition at the level of the sympathetic nerve ending appears to be a class effect of the AT1-receptor blockers, mediated by presynaptic AT1-receptors. With respect to the ratio pre-/postsynaptic AT1-receptor antagonism important quantitative differences between the various compounds were found. 4 Both the pre- and postjunctional receptors at the sympathetic nerve endings belong to the AT1-receptor population. However, the presynaptic receptors belong to the AT1B-subtype, whereas the postjunctional receptors probably belong to a different AT1-receptor subpopulation. 5 Sympatho-inhibition is a class effect of the AT1-receptor antagonists. In conditions in which the SNS plays a pathophysiological role, such as hypertension and congestive heart failure, this property may well be of therapeutic relevance.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 103 (1980), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Serum levels of 8-methoxypsoralen were determined in six human volunteers after two different methods of oral administration.8-Methoxypsoralen was given as an aqueous solution and as powder in gelatin capsules. The area under the curve (AUC) values were higher (P 〈 0.05) for the solution than for the capsules, indicating a higher bioavailability. Also, the peak serum levels were higher and were reached earlier when given as a solution. Considerable individual variation of the maximum serum levels and the area under the curve values was observed for both methods of administration, but the time required to reach the maximum serum level was more predictable after administration of the solution.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 522 (1988), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1912
    Keywords: Calcium handling ; α1-adrenoceptors ; Hyperthyroidism ; Hypothyroidism ; Tissue catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated the influence of hyper- and hypothyroidism on basal parameters of isolated perfused hearts of rats. In addition the effects of different extracellular calcium concentrations ([Ca2+]o), the calcium entry promoter Bay K8644 and the α1-adrenoceptor agonist methoxamine were investigated. Since alterations in α-adrenoceptor density could explain the increased sensitivity to methoxamine in hearts from hypothyroid rats, α1-adrenoceptor density in the left ventricle was also established. Different time-schedules of exposure to hyper- and hypothyroidism were used to investigate whether the influence of chronic dysthyroid states on α1-adrenoceptor density is transient and time-dependent. Simultaneously myocardial noradrenaline and adrenaline tissue concentrations were determined, since they might correlate with the observed changes. Hyperthyroidism was induced by feeding rats for 1, 4 and 8 weeks with 5 mg/kg L-thyroxine (T4)-containing rat chow. Hypothyroid rats were obtained by adding 0.05% propylthiouracil (PTU) to the drinking water during 1, 4 and 8 weeks. For the functional experiments animals were treated during 4 weeks, to mimic the clinical situation of a chronic endocrine disease. Langendorff hearts from hyperthyroid hearts showed an increased maximally developed relaxation velocity, whereas Langendorff hearts from hypothyroid rats showed an increased left ventricular pressure (LVP). We observed an increased maximal inotropic response to [Ca2+]o in hearts from both hyperthyroid and hypothyroid rats, indicating that both dysthyroid states interfere with the handling of calcium ions by the contractile apparatus. Unchanged responses to Bay K8644 in hearts from hyperthyroid and depressed responses in hearts from hypothyroid rats suggest that the involvement of L-type calcium channels is rather unlikely. Furthermore, the reflex increase in coronary flow in response to enhanced contractile force appeared to fail in hearts from hypothyroid rats. Sensitivity of the response to methoxamine was increased in hearts from hypothyroid rats, which was accompanied by a decrease in the number of myocardial α1-adrenoceptors. Both T4 and PTU treatment resulted in a non-transient decrease of α1-adrenoceptor density in left ventricular tissue. Furthermore, hypothyroidism increased the percentage of α1A-binding sites, whereas in hyperthyroidism the distribution of the α1-adrenoceptor subtypes was not affected. Myocardial tissue concencentrations of noradrenaline and adrenaline were unchanged in hyperthyroid rats and decreased in hypothyroid rats. The present study indicates that thyroid hormones have a direct rather than a sympathetically mediated effect on α1-adrenoceptor mediated myocardial functions.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2013
    Keywords: Parathormone ; Vitamin D3 ; Hypercalcaemia ; Blood pressure ; Nitedipine ; Hydralazine ; Conscious rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of a chronically elevated total plasma calcium concentration on blood pressure and heart rate was investigated in conscious normotensive rats. The plasma calcium concentration was elevated by continuous subcutaneous infusion with parathormone (PTH) after parathyreoidectomy, and by oral treatment with vitamin D3. In both groups an elevated blood pressure was observed at the 1st day of treatment only. Blood pressure was returned to pretreatment values from the second day of treatments onaards. No significant changes in heart rate, due to hypercalcaemia, were observed. In hypercalcaemic rats, the calcium entry inhibitor nifedipine proved more potent in reducing blood pressure than in normocalcaemic control animals. Hydralazine was equipotent in reducing blood pressure in both groups. It is suggested, that the vasoconstrictor effects of a chronically elevated total plasma calcium concentration in conscious rats does not obviously result in a chronically elevated blood pressure, but rather in an enhanced sensitivity of the blood pressure towards calcium entry blockade.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 253 (1966), S. 310-326 
    ISSN: 1432-1912
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary 1. The effects of centrally administered reserpine on the blood pressure, on the carotid reflexes [carotid occlusion reflex (COR); its baroreceptor and chemoreceptor component; chemoreceptor reflex] and on the catecholamine content of brain, heart, and aorta were investigated in cats under chloralose anesthesia. Reserpine was injected into the vertebral artery by means of a polyethylene catheter inserted into the brachial or subclavian artery. 2. Reserpine, injected in a dose of 80 μg/kg into the vertebral artery, significantly lowered the noradrenaline (and often the dopamine) content of the brain 5 hrs, but not 2 hrs after administration. By contrast, reserpine did not reduce the catecholamine content of the heart or the aorta at any time. These results were taken as evidence that under our experimental conditions reserpine acted predominantly centrally. 3. The injection of 80 μg/kg reserpine into the vertebral artery lowered the blood pressure and decreased the COR by more than 50% after a latent period of 2–3 hrs. The maximum decrease in the COR occurred 5 hrs after reserpine. In no experiment was a complete abolition of the reflex obtained. The decrease in the COR did not seem to depend on a lowering of the blood pressure and was not influenced by adrenalectomy. 4. It was shown that reserpine decreased the COR by selectively decreasing and finally abolishing the chemoreceptor component, the baroreceptor component being unaffected throughout the experiment. Reserpine also abolished the chemoreceptor reflex, which was elicited by local injection of potassium cyanide. 5. The effects of reserpine on the carotid sinus reflexes were paralleled to some extent by its effects on the catecholamine level in the brain. 6. l-DOPA, 0.5 mg/kg, administered centrally, increased the COR in untreated animals after a latent period of about 1/2 hr. l-DOPA did not antagonize the reserpine-induced decrease in the COR. dl-5-HTP, injected centrally, had no consistent action on the COR. 7. The results seem to indicate that, under suitable experimental conditions, reserpine acts centrally to produce a lowering of the blood pressure and an inhibition of some of the carotid reflexes. Central adrenergic mechanisms might be involved in the reserpine effects examined.
    Notes: Zusammenfassung 1. An Katzen in Chloralose-Narkose wurde die Wirkung von zentral verabreichtem Reserpin auf Blutdruck, Carotissinus-Reflexe [Carotissinus-Entlastungsreflex (CSER), seine Baro- und Chemoreceptorkomponente sowie Chemoreceptorreflex] und auf den Katecholamingehalt in Gehirn, Herz und Aorta untersucht. Die Zufuhr von Reserpin erfolgte in die A. vertebralis über einen A. brachialis- bzw. A. subclavia-Katheter. 2. Die Gabe von 80 μg/kg Reserpin in die A. vertebralis erniedrigte nach 5 Std, nicht jedoch nach 2 Std signifikant den Noradrenalin- und oft auch den Dopamingehalt des Gehirnes, ließ jedoch den Katecholamingehalt des Herzens und der Aorta unbeeinflußt. Dieses unterschiedliche Verhalten der Katecholamine im Gehirn einerseits und im Herzen und in der Aorta andererseits läßt darauf schließen, daß Reserpin bei unserer Versuchsanordnung praktisch nur zentral gewirkt hat. 3. Die Gabe von 80 μg/kg Reserpin in die A. vertebralis führte nach einer Latenzzeit von 2–3 Std zu einer Blutdrucksenkung und ebenfalls nach einer Latenzzeit von 2–3 Std zu einer Abschwächung des CSER um mehr als 50% der Norm, die etwa nach 5 Std das Maximum aufwies; es kam jedoch nie zu einer völligen Aufhebung des CSER. Die Abschwächung des CSER war nicht vom Auftreten einer Blutdrucksenkung abhängig und wurde durch Adrenalektomie nicht beeinflußt. 4. Es konnte gezeigt werden, daß die reserpinbedingte Abschwächung des CSER ihre Ursache in einer Abschwächung und schließlich völligen Aufhebung der Chemoreceptorkomponente hatte, während die Baroreceptorkomponente durch Reserpin nicht abgeschwächt wurde. Der durch lokale Applikation von KCN ausgelöste Chemoreceptorreflex wurde ebenfalls durch Reserpin abgeschwächt und aufgehoben. 5. Zwischen den Reserpineffekten auf die Carotissinus-Reflexe und auf den Katecholamingehalt des Gehirnes lassen sich gewisse Parallelen feststellen. 6. Die zentrale Verabreichung von 0,5 mg/kg l-DOPA führte an unbehandelten Tieren nach einer Latenzzeit von meist etwa 1/2 Std zu einer Verstärkung des CSER; die reserpinbedingte Abschwächung des CSER wurde durch l-DOPA nicht beeinflußt. Die zentrale Gabe von dl-5-HTP hatte keinen eindeutigen Effekt auf den CSER. 7. Die Ergebnisse lassen das Vorhandensein von rein zentralen Wirkungen des Reserpins auf Blutdruck und Carotissinus-Reflexe erkennen und machen eine Beteiligung von zentral-adrenergen Mechanismen an diesem Geschehen wahrscheinlich.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 249 (1964), S. 446-454 
    ISSN: 1432-1912
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Zusammenfassung Das System mesencephale Formatio reticularis — Septum — Hippocampus bildet funktionell insofern eine Einheit, als die retikulären Impulse die Septumzellen veranlassen, in rhythmischen Gruppen (Bursts) zu entladen, die die Bildung von Thetawellen im Hippocampus anregen. Die Wirkung von Urethan auf dieses System wurde an Kaninchen mit Mikro- und Makroelektroden untersucht. Unter Urethan nimmt die Entladungsrate der Septumzellen pro Minute und pro Burst ab, die mittlere Burstperiode der rhythmischen Septumzellentladungen nimmt zu. Die Septumzellen entladen selbst dann noch rhythmisch in Bursts, wenn im Hippocampus kein Thetarhythmus mehr vorhanden ist. Ableitungen mit Nadelelektroden aus dem Hippocampus und Cortex im Verlauf der Urethannarkose zeigten, daß im Gegensatz zu Barbituraten in tiefster Narkose immer wieder Stadien von paradoxem Schlaf auftreten, gekennzeichnet durch Aktivierung einer hohen, regelmäßigen Thetatätigkeit im HC und Abflachung des Rinden-EEGs. Nach diesen Befunden ist anzunehmen, daß Urethan das limbische System nur in geringem Grade beeinflußt: Zuerst werden die synaptischen Mechanismen im Hippocampus gehemmt und erst später die Septumzellen. Auf die Formatio reticularis dürfte Urethan, wenn überhaupt, so nur einen geringen Einfluß haben, da selbst in tiefster Narkose noch Perioden paradoxen Schlafes auftreten.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 250 (1965), S. 291-292 
    ISSN: 1432-1912
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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