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  • Anaesthetized rabbit  (2)
  • Indirect sympathomimetic amines  (2)
  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 342 (1990), S. 469-476 
    ISSN: 1432-1912
    Schlagwort(e): Anaesthetized rabbit ; Noradrenaline spillover rate ; Sympathoinhibition ; Sympathetic nerve activity ; Uptake inhibition
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The aim of the study was to determine the sites of action of intravenously administered desipramine on the sympathetic nervous system in anaesthetized rabbits (alfadolone + alfaxalone). Renal postganglionic sympathetic nerve activity was measured in order to determine central nervous and ganglionic effects. The clearance of noradrenaline from the plasma was determined with an isotope tracer method. From the noradrenaline clearance and the plasma concentration of noradrenaline the noradrenaline spillover rate was calculated. These parameters as well as blood pressure and heart rate were measured before (basal values) and at the end of 20-min infusions of sodium nitroprusside, which was given in order to modulate efferent sympathetic nerve activity through the baroreceptors. Desipramine 0.5 mg kg-1 + 0.05 mg kg−1 h−1 (bolus injection followed by infusion) and 2 mg kg−1 + 0.2 mg kg−1 h−1 dose-dependently inhibited basal sympathetic nerve activity and the noradrenaline clearance. Desipramine had no effect on basal blood pressure, noradrenaline spillover rate or heart rate. Nitroprusside produced hypotension and simultaneously increased sympathetic nerve activity, noradrenaline spillover rate and heart rate; the clearance of noradrenaline was reduced with decreasing blood pressure. The relationship between sympathetic nerve activity and blood pressure was shifted by desipramine in a manner indicating central sympathoinhibition. Desipramine had no effect on the relationship of the noradrenaline spillover rate to blood pressure, whereas it shifted the heart rate-blood pressure relationship in a manner indicating an enhancement of reflex cardioacceleration. In a separate series of experiments, desipramine also inhibited sympathetic nerve activity in baroreceptor-denervated animals. The results show that desipramine centrally inhibits sympathetic outflow in the rabbit. Simultaneously, it enhances the noradrenaline spillover per action potential peripherally. In our study, the two effects compensated for each other, so that desipramine had no major effect on the relationship between noradrenaline spillover and blood pressure. In the heart, the peripheral effect of desipramine outweighed the central sympathoinhibition, hence the reflex cardioacceleration.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 353 (1996), S. 175-183 
    ISSN: 1432-1912
    Schlagwort(e): Key words Guinea-pig vas deferens ; Noradrenaline release ; ATP release ; Cotransmission ; Tyramine ; Indirect sympathomimetic amines
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Contractions, release of noradrenaline and release of ATP elicited by the indirectly acting sympathomimetic amine tyramine and responses elicited by exogenous noradrenaline were studied in the isolated vas deferens of the guinea pig. Release of noradrenaline was assessed as overflow of tritium after preincubation with [3H]-noradrenaline. ATP was measured by means of the luciferin-luciferase technique. In tissues pretreated with pargyline 1 mM, tyramine 300 μM, when added to the superfusion medium for 2 min, elicited contraction and an overflow of tritium (mainly [3H]-noradrenaline) and ATP. Contraction and ATP overflow responses were prevented and tritium overflow was greatly reduced by desipramine 10 μM. Prazosin 0.3 μM abolished contractions and evoked ATP overflow without changing tritium overflow. Blockade of postjunctional P2-purinoceptors by suramin 300 μM caused a marked decrease of tyramine-evoked contractions and a slight reduction of tritium overflow whereas evoked ATP overflow was markedly increased. The effect on contraction was not shared by two other P2-purinoceptor antagonists, namely pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) 32 μM and diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS) 32 μM: PPADS increased contractions about fourfold, whilst DIDS had no effect at all. When the vas deferens was superfused for 24 min with medium containing tyramine 300 μM, evoked contractions and tritium overflow continued throughout whereas ATP overflow faded rapidly to basal values. In the presence of prazosin 0.3 μM, tyramine 300 μM again failed to elicit contractions as well as an overflow of ATP. Application of noradrenaline 10 μM instead of tyramine also resulted in prolonged contraction and an overflow of ATP that declined rapidly. It is concluded that all ATP released by tyramine is non-neuronal in origin, secondary to the activation of postjunctional α1-adrenoceptors by released noradrenaline. The non-neural ATP does not seem to play a functional role in smooth muscle contraction and derives from a postjunctional source which is subject to a rapid depletion upon sustained α1-adrenoceptor activation.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 353 (1996), S. 175-183 
    ISSN: 1432-1912
    Schlagwort(e): Guinea-pig vas deferens ; Noradrenaline release ; ATP release ; Cotransmission ; Tyramine ; Indirect sympathomimetic amines
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Contractions, release of noradrenaline and r elease of ATP elicited by the indirectly acting sympathomimetic amine tyramine and responses elicited by exogenous noradrenaline were studied in the isolated vas deferens of the guinea pig. Release of noradrenaline was assessed as overflow of tritium after preincubation with [3H]-noradrenaline. ATP was measured by means of the luciferin-luciferase technique. In tissues pretreated with pargyline 1 mM, tyramine 300 μM, when added to the superfusion medium for 2 min, elicited contraction and an overflow of tritium (mainly [3H]-noradrenaline) and ATP. Contraction and ATP overflow responses were prevented and tritium overflow was greatly reduced by desipramine 10 μM Prazosin 0.3 μM abolished contractions and evoked ATP overflow without changing tritium overflow. Blockade of postjunctional P2-purinoceptors by suramin 300 μM caused a marked decrease of tyramine-evoked contractions and a slight reduction of tritium overflow whereas evoked ATP overflow was markedly increased. The effect on contraction was not shared by two other P2-purinoceptor antagonists, namely pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) 32 μM and diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS) 32 μM: PPADS increased contractions about fourfold, whilst DIDS had no effect at all. When the vas deferens was superfused for 24 min with medium containing tyramine 300 μM, evoked contractions and tritium overflow continued throughout whereas ATP overflow faded rapidly to basal values. In the presence of prazosin 0.3 μM, tyramine 300 μM again failed to elicit contractions as well as an overflow of ATP. Application of noradrenaline 10 μM instead of tyramine also resulted in prolonged contraction and an overflow of ATP that declined rapidly. It is concluded that all ATP released by tyramine is non-neuronal in origin, secondary to the activation of postjunctional α1-adrenoceptors by released noradrenaline. The non-neural ATP does not seem to play a functional role in smooth muscle contraction and derives from a postjunctional source which is subject to a rapid depletion upon sustained α1-adrenoceptor activation.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 340 (1989), S. 648-657 
    ISSN: 1432-1912
    Schlagwort(e): Anaesthetized rabbit ; Blood pressure ; Plasma noradrenaline concentration ; Presynaptic α2-autoreceptors ; Sympathetic nerve activity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The function of presynaptic α2-autoreceptors at postganglionic sympathetic neurones under conditions of normal, ongoing sympathetic impulse traffic was studied in anaesthetized rabbits (alfadolone + alfaxalone). Clonidine was used as an α2-adrenoceptor agonist, and yohimbine and rauwolscine were used as antagonists. Mean arterial pressure, postganglionic renal sympathetic firing rate, arterial plasma noradrenaline concentration and heart rate were measured before (basal values) and at the end of 3-min infusions of sodium nitroprusside and phenylephrine, which were given to modulate efferent activity in the sympathetic nervous system through the baroreflex. The nitroprusside- and phenylephrine-induced changes of mean arterial pressure produced the expected changes in sympathetic nerve activity, plasma noradrenaline and heart rate. Clonidine (5 µg kg−1 + 0.5 µg kg−1 min−1) reduced the basal mean arterial pressure, sympathetic nerve activity and heart rate. It also reduced the nitroprusside-induced increase in the plasma noradrenaline level without changing the nitroprusside-induced increase in sympathetic firing. These results, as well as the mean arterial pressure-sympathetic nerve activity and the sympathetic nerve activity-plasma noradrenaline function curves indicate that clonidine inhibited both sympathetic tone centrally and the average release of noradrenaline per action potential peripherally. Yohimbine (1 mg kg−1 + 0.1 mg kg−1 h−1) and rauwolscine (0.5 mg kg−1 + 0.1 mg kg−1 h−1) increased the basal plasma noradrenaline level without any increase of renal sympathetic nerve activity. They also enhanced the nitroprusside-induced increase in plasma noradrenaline without any enhancement of the nitroprusside-induced increase in sympathetic firing. The hypotensive response to nitroprusside was attenuated, whereas the heart rate response was augmented. These results, as well as the mean arterial pressure-sympathetic nerve activity and the sympathetic nerve activity-plasma noradrenaline function curves indicate that the main effect of yohimbine and rauwolscine was to increase the average release of noradrenaline per action potential. The simultaneous measurement of postganglionic sympathetic nerve activity and the arterial plasma noradrenaline concentration proved suitable to differentiate central (or ganglionic; this distinction was not possible) effects of α2-adrenoceptor ligands from peripheral presynaptic effects. The results show that endogenous presynaptic, α2-adrenergic autoinhibition of noradrenaline release from postganglionic sympathetic neurones operates physiologically in anaesthetized rabbits with ongoing, uninterrupted sympathetic nerve activity. The results also indicate that blockade of α2-autoreceptors enhances the sympathetic reflex compensatory response to a hypotensive stimulus.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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