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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochimica et Biophysica Acta (BBA)/Biomembranes 512 (1978), S. 415-428 
    ISSN: 0005-2736
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1424
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The permeation of various cations and biogenic amines across artificial lipid membranes (bilayer membranes) was investigated by means of electrical conductivity measurements and fluorescence spectroscopy. Their permeability properties were modified by doping them with five different carboxylic ionophores. The induced permeability changes were correlated with some biological activities of the ionophores. Four out of five ionophores increased the permeability of doped membranes for Li+, Na+, K+, Mg2+ and Ca2+. Two of them showed a preference for K+ whereas one (X-537A) increased the membrane permeability for K+ as well as for Ca2+. It was also found that the ionophores increased the permeability for serotonin, dopamine, norepinephrine and epinephrine. No direct coupling was found between the facilitated ion permeation and the permeation of biogenic amines induced by the ionophores. The measurements can be qualitatively explained by assuming that the permeation of biogenic amines is competitively inhibited by cations. It appears that one biogenic amine molecule forms a complex with one ionophore molecule, the complex acting as a carrier for biogenic amines. All ionophores investigated increased the bilayer permeability considerably for some biogenic amines. (A preference up to 420∶1 for serotonin over epinephrine was measured for one specific ionophore.) There was no correlation between thein vitro antibacterial activity (against bacillus E and bacillus TA) of the ionophores and their potency to change the ion permeability of doped membranes. The correlation found between the ionophore-induced permeation of biogenic amines through membranes and their antibacterial activity is probably without biological meaning. However, a rather good correlation was found between cardiac sympathetic effects of the ionophores and their ability to facilitate permeation of norepinephrine through artificial membranes.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 264 (1969), S. 241-243 
    ISSN: 1432-1912
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 285 (1974), S. 1-14 
    ISSN: 1432-1912
    Keywords: Clonidine ; Baroreceptor Reflex ; Sympathetic Nerve Activity ; Blood Pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The relationship between the central action of the hypotensive drug clonidine and the depressor baroreceptor reflex was studied in cats anaesthetized with urethane. Activation of the depressor baroreceptor reflex was achieved by bilateral electrical stimulation of the sinus nerves. The magnitude of the activation of the reflex was estimated from the resultant decrease in spontaneous sympathetic activity recorded from the preganglionic splanchnic and a postganglionic renal nerve and from the subsequent fall in blood pressure. The effect of bilateral sinus nerve stimulation was frequency-dependent over the range of 2 to 32 shocks/sec and allowed the construction of frequency-response curves. Clonidine in low doses (1 and 3 μg/kg i.v.), which caused no or only a slight depression of spontaneous sympathetic nerve activity and of the blood pressure, increased the response to bilateral sinus nerve stimulation with a resultant shift of the respective frequency-response curves to lower rates of stimulation. Clonidine also augmented the bradycardia produced by an activation of the depressor baroreceptor reflex. These results indicate a facilitation of the depressor baroreceptor reflex by clonidine. While the increase in activity of the splanchnic and renal sympathetic nerves and the rise in blood pressure due to hypothalamic stimulation were reduced by simultaneous bilateral sinus nerve stimulation or by an injection of clonidine, the evoked contractions of the nictitating membranes remained uninfluenced by both procedures. Thus, the effect of clonidine resembles an activation of the depressor baroreceptor reflex in inhibiting preferentially the activity in adrenergic vasomotor fibres. This and the clonidine-induced facilitation of the reflex suggest an intimate relationship between the action of clonidine and an activation of the central pathway of the depressor baroreceptor reflex.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 263 (1969), S. 217-218 
    ISSN: 1432-1912
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 265 (1969), S. 260-277 
    ISSN: 1432-1912
    Keywords: Bretylium ; Adrenergic Nerve Blockade ; Local Anaesthetic Action ; Adrenergic Nerve Ending ; Asynchronous Discharge ; Bretylium ; Blockade der adrenergen Nervenendigungen ; Lokalanaesthetische Wirkung ; Adrenerge Nervenendigungen ; Asynchrone Entladungen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Bretylium and tetracaine when perfused at increasing concentrations inhibited and finally blocked discharges elicited by acetylcholine and KCl in adrenergic nerve endings of the isolated perfused heart and less regularly in the isolated perfused spleen of the cat. There was a direct correlation between the inhibition of the effects of sympathetic nerve stimulation and the inhibition of KCl-induced discharges by bretylium and tetracaine in the heart with regard to both intensity and time course. Acetylcholine-induced release of noradrenaline in the heart was somewhat more resistant to the action of bretylium than acetylcholine-induced antidromic discharges in cardiac adrenergic nerves. Bretylium and tetracaine inhibited and blocked discharges in sinus nerve afferents elicited by rises in the perfusion pressure and by injection of KCl. The concentration for complete block in the perfused carotid sinus preparation was 800–1,000 times higher for bretylium than for tetracaine, whereas bretylium was equally or more potent (depending on the time of interaction) than tetracaine in the isolated perfused heart. Moreover, the effect of bretylium in the heart and spleen developed slowly, increased continuously during the perfusion period and was very resistant to washing out. In contrast, tetracaine achieved its maximum effect on heart, spleen and carotid sinus preparations very rapidly and was readily washed out. The time course and reversibility of the effect of bretylium on baroreceptor afferents were not drastically different from those of tetracaine. All observations may be explained by the fact that bretylium is a very weak local anaesthetic causing, however, a marked selective local anaesthesia of adrenergic nerve terminals because of its high accumulation in these endings. The adrenergic nerve blocking effect of bretylium seems to be adequately explained by its stabilizing effect on the membrane of the nerve terminals.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 266 (1970), S. 18-33 
    ISSN: 1432-1912
    Keywords: Genetically Hypertensive Rats ; Renal Hypertensive Rats ; Isolated Mesenteric Arteries ; Noradrenaline ; KCl ; Genetisch hypertone Ratten ; renal hypertone Ratten ; isolierte Mesenterialarterien ; Noradrenalin ; KCl
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Vasoconstrictor responses to noradrenaline, KCl and periarterial nerve stimulation were studied in isolated mesenteric artery preparations from normotensive, genetically hypertensive and renal hypertensive rats. Innormotensive rats sympathetic denervation or cocaine produced a shift of the dose-response curve for noradrenaline to the left by a factor of approximately 3 but did not alter the dose-response curve for KCl; in denervated arteries cocaine did not affect the dose-response curve for noradrenaline. Cocaine failed to increase the effect of periarterial nerve stimulation. The degree of denervation supersensitivity to noradrenaline was the same 3 to 5 days or 3 to 4 weeks after removal of the coeliac ganglion. Prolonged treatment of rats with the ganglion blocking agent chlorisondamine did not alter the sensitivity of the isolated mesenteric arteries to noradrenaline. These results suggest the occurrence of a prejunctional supersensitivity in the rat mesenteric arteries, but give no indication of the development of a postjunctional supersensitivity after chronic interruption of adrenergic transmitter release. Mesenteric arteries isolated fromgenetically hypertensive rats of a Japanese strain were supersensitive to noradrenaline and KCl and the maximal response to both agents was increased. Cocaine or denervation did not further increase the supersensitivity of these vessels. The vessels responded approximately 3 times more strongly to periarterial nerve stimulation than those of normotensive controls. Dose-response curves for noradrenaline obtained inexperimental renal hypertensive rats were shifted to the left by a factor of 3 as compared with normotensive controls and their maximum was elevated. However, the response to periarterial nerve stimulation was the same as in normotensive rats. In both genetically and renal hypertensive rats the arterial blood pressure and the sensitivity of the isolated mesenteric arteries to noradrenaline seemed to be correlated. No difference in noradrenaline content of the mesentery could be found between normotensive and hypertensive rats.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 274 (1972), S. 211-228 
    ISSN: 1432-1912
    Keywords: Central Adrenergic Neurons ; Blood Pressure ; Heart Rate ; DOCA/NaCl Hypertensive Rats ; Spontaneously Hypertensive Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 6-Hydroxydopamine (6-OH-DA) was injected into the left lateral brain ventricle of normotensive, DOCA/NaCl or spontaneously hypertensive rats, and its effect on heart rate and blood pressure was studied. A single injection of 250 μg 6-OH-DA or 3 successive administrations of the same dose caused a reduction of noradrenaline content and tyrosine hydroxylase activity in several parts of the brain to 10–50% of the control values, indicating a considerable destruction of central adrenergic neurons. Heart rate and blood pressure decreased within 10 to 20 min after a single intraventricular injection of 6-OH-DA and both parameters returned to normal after 7 h. This effect was equally observed in normotensive and both types of hypertensive rats and regardless of whether the animals were conscious or anaesthetized. It was prevented by a prior intraventricular injection of phentolamine; this suggests that it is mediated by central alpha-adrenoceptors. The 6-OH-DA-induced bradycardia and hypotension were not influenced by a blockade of peripheral muscarinic receptors with scopolamine methylbromide; however, they were accompanied by a decrease of spontaneous discharges in the splanchnic nerve and, therefore, seem to be due to a reduction in peripheral sympathetic tone. The early cardiovascular effects of 6-OH-DA were sometimes followed by a second phase of bradycardia and hypotension. It occurred in normotensive rats 1–2 days after the second or third intraventricular injection of 6-OH-DA, and in spontaneously hypertensive rats already after a single injection. The hypotension of the second phase lasted 5–6 days, the bradycardia showed no recovery during the observation period which was limited to 3 weeks. Such long term cardiovascular effects of intraventricular 6-OH-DA were never observed in DOCA/NaCl hypertensive rats even after repeated administrations of the compound. The results provide evidence for the existence of a central adrenergic regulation of blood pressure and heart rate which seems to differ in normotensive and hypertensive rats.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 286 (1974), S. 97-111 
    ISSN: 1432-1912
    Keywords: Clonidine ; Central Presynaptic α-Adrenoceptors ; Central Post-synaptic α-Adrenoceptors ; Noradrenaline Release ; Sympathetic Nerve Activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of clonidine on blood pressure, heart rate, contractile state of the nictitating membranes, spontaneous sympathetic nerve activity and response of sympathetic nerves to hypothalamic stimulation were compared in normal anaesthetized cats and in anaesthetized cats pretreated with reserpine and α-methyl-p-tyrosine. The pretreatment lowered the noradrenaline content of various parts of the brain to less than 5 ng/g, i.e. to less than 1–3% of that of the controls. Under the conditions of this severe noradrenaline depletion, blood pressure and heart rate were low and spontaneous sympathetic nerve activity consisted of continous, high-amplitude discharges which contrasted with the low-amplitude bursts of activity—synchronous with the respiration—of the controls. In contrast to the controls, clonidine did not lower blood pressure and heart rate in the cats with noradrenaline depletion; however, the clonidine-induced contractions of the nictitating membranes were of similar magnitude and duration in both groups of animals. The efficacy of clonidine in reducing or abolishing spontaneous sympathetic nerve activity and in inhibiting the response of sympathetic nerves to hypothalamic stimulation was equal in controls and in cats with noradrenaline depletion, its potency being 3-fold higher in the former. The results indicate a direct stimulation of α-adrenoceptors by clonidine both in the periphery and in the central nervous system and make it unlikely that the central effect of clonidine on blood pressure is due to a release of noradrenaline from central adrenergic neurones. It is further concluded that clonidine activates an adrenergic mechanism in the central nervous system by stimulation of postsynaptic α-adrenoceptors. The inhibition of such a mechanism as a consequence of a diminished noradrenaline release due to stimulation of presynaptic α-adrenoceptors—as proposed from in vitro experiments—seems to be of no importance for the central effect of clonidine on sympathetic nerve activity and blood pressure.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 278 (1973), S. 231-246 
    ISSN: 1432-1912
    Keywords: Clonidine ; Sympathetic Nerve Activity ; Blood Pressure ; Baroreceptor Reflex ; Central α-Adrenoceptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Arterial blood pressure, heart rate and discharges in the preganglionic splanchnic and a postganglionic renal sympathetic nerve were recorded in cats anaesthetized with urethane. Electrical stimulation of the posterior hypothalamus or the fastigial nucleus of the cerebellum elicited an immediate increase in sympathetic nerve activity and a rise in blood pressure and heart rate. The stimulation-induced discharge pattern in the sympathetic nerves was characterized by a strong initial burst followed by a phase of inhibition and a final stabilization of the discharges at a level definitely lower than the initial burst. This pattern was reversibly converted into a constant high amplitude firing during a lowering of the blood pressure by bleeding the cats and irreversibly so after cutting the buffer nerves. These findings indicate that the inhibitory phase of the sympathetic discharge pattern during central stimulation is due to the rise in blood pressure and the ensuing baroreceptor-reflex activation. Clonidine (0.03 and 0.1 mg/kg i.v.) reduced the spontaneous sympathetic nerve activity and lowered blood pressure and heart rate. The sympathetic discharges evoked by central stimulation were partially inhibited by clonidine, an effect which could be overcome by raising the voltage used for central stimulation. Independent of the strength of this stimulation an inhibitory phase in the evoked discharge pattern was not observed after clonidine, even when the low blood pressure due to the drug action was raised by a noradrenaline infusion. After clonidine, the evoked discharge pattern closely resembled that after simultaneous stimulation of both sinus nerves and the hypothalamus or the fastigial nucleus, and it was not altered by additional stimulation of the sinus nerves. These observations have led to the hypothesis that clonidine causes a long-lasting activation within an as yet unidentified part of the central pathway of the depressor baroreceptor reflex. In view of the well-known α-adrenoceptor stimulating property of clonidine, and since the central effect of clonidine was antagonized by the α-adrenoceptor blocking agent piperoxan, it is likely that the central part of the baroreceptor-reflex pathway is modified by or contains adrenergic neurones.
    Type of Medium: Electronic Resource
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