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  • Isoprenaline  (3)
  • Rabbit papillary muscle  (3)
  • 1
    ISSN: 1432-1912
    Schlagwort(e): Papaverine ; Isoprenaline ; cAMP ; Contractility ; Frequency of stimulation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Responses to papaverine and isoprenaline on cyclic AMP and contractility were investigated in left atria of guinea-pigs driven at a rate of 0.5 or 2 Hz. 1. Studies on the time course of the effects of isoprenaline (3×10−8 M) showed that the increase in cAMP levels preceded the increase in contractile activity. cAMP increased to maximal values and then rapidly fell to the control levels with a similar time course both at 0.5 and 2 Hz. The contractile responses to isoprenaline, however, showed a different time course. The development of the inotropic response to isoprenaline occurred faster at 2 Hz than at 0.5 Hz. In contrast to the levels of cAMP maximal contractile responses were maintained throughout the presence of isoprenaline. 2. At a stimulation frequency of 2 Hz with increasing concentrations of papaverine (10−6 M, 3×10−6 M, 3×10−5 M) the cAMP content increased dose-dependently. However, no correlation between the effects on cAMP and contractility could be established since 3×10−5 M papaverine already reduced contractile amplitude. The same concentration of papaverine slightly depresssed the inotropic responses to isoprenaline whereas it considerably enhanced the effects of isoprenaline on cAMP. 3. At a stimulation frequency of 0.5 Hz papaverine produced similar effects on the basal cAMP level and the cAMP responses to isoprenaline as at 2 Hz. However, papaverine increased significantly cardiac contractility and potentiated the positive inotropic effects of isoprenaline. At this rate of stimulation a linear relationship between the positive inotropic effect and the increase in cAMP as produced by increasing concentrations of papaverine (10−6 M, 3×10−6 M, 3×10−5 M) was obtained. The dissociation of the effects of papaverine on contractility and cAMP seems to be related to a calcium antagonistic property which—in addition to the inhibition of phosphodiesterase—comes into play at higher rates of beat and inhibits the effects of elevated cAMP on myocardial contractility.
    Materialart: Digitale Medien
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 320 (1982), S. 152-159 
    ISSN: 1432-1912
    Schlagwort(e): α- and β-Adrenoceptors ; Positive inotropic effect ; Acetylcholine ; Accentuated antagonism ; Rabbit papillary muscle
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The influence of acetylcholine (ACh) on the positive inotropic responses to α- as well as β-adrenoceptor stimulation was investigated in the isolated electrically driven rabbit ventricular muscle. 1. Stimulation of muscarinic receptors by ACh (10−9–10−4 mol/l) reduced the positive inotropic effect evoked by isoprenaline (10−8 mol/l) via β-adrenoceptor stimulation, but enhanced the positive inotropic effect of the α-adrenoceptor stimulating agent phenylephrine (10−6 mol/l) in the presence of pindolol (3×10−8 mol/l). 2. Sodium nitroprusside (SNP) (10−6–10−3 mol/l) reduced the β-adrenoceptor-mediated positive inotropic effect but did not effect the α-adrenoceptor-mediated one. 3. The depression by ACh (10−6 mol/l) or SNP (10−4 mol/l) of the positive inotropic effects evoked by β-adrenoceptor stimulation was accompanied by a decrease of the cAMP level which has been elevated by isoprenaline. However, the enhancement of the α-adrenoceptor mediated positive inotropic effect by ACh seems to be independent of changes in cAMP- and/or cGMP-levels. 4. ACh (10−6 mol/l) diminished the shortening of the action potential duration induced by isoprenaline (10−8 mol/l) in Tyrode solution and Ca2+-dependent potential restored by β-adrenoceptor stimulation in 27 mmol/l K+ Tyrode solution. In contrast, ACh (10−6 mol/l) affected neither the prolongation of action potential duration nor the Ca2+-dependent potential caused by α-adrenoceptor stimulation. The depression by acetylcholine of the β-adrenoceptor mediated positive inotropic effect may be due to the decrease in cAMP content and to the reduction of the slow inward current while the enhancement by ACh of the α-adrenoceptor mediated positive inotropic effect is not associated with changes in cAMP- and/or cGMP-levels and in electrophysiological phenomena. It is concluded that the accentuated antagonism (Levy 1971) between sympathomimetic and parasympathomimetic agents at the postsynaptic region results mainly from the interaction between β-adrenoceptor- and muscarinic receptor-mediated responses, and that the α-adrenoceptor-mediated responses are able to counteract the accentuated antagonism.
    Materialart: Digitale Medien
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  • 3
    ISSN: 1432-1912
    Schlagwort(e): α-and β-Adrenoceptors ; Methoxamine ; Isoprenaline ; cAMP ; Papaverine ; Rabbit Papillary Muscle
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In the isolated papillary muscle of the rabbit the time course of the effects of selective β-and α-adrenoceptor stimulation by isoprenaline and methoxamine, respectively, on the contractile force and on the level of 3′,5′-cyclic AMP (cAMP) was determined. 1. Isoprenaline (3×10−7 M) increased significantly the content of cAMP at 15 sec and elevated it to the maximal level-about twice the control value-at 30 sec after its administration, while the developed tension of the papillary muscle was also increased significantly at 15 sec and reached gradually its maximum at 90 sec. 2. Compared with isoprenaline methoxamine (10−4 M) increased the developed tension very slowly: the maximal response was reached after 20 min. The level of cAMP, on the other hand, was changed neither before nor during the induction of the positive inotropic effect of methoxamine. 3. The phosphodiesterase inhibitor papaverine (10−5 M) inhibited the PDE activity of the papillary muscle by about 40% after an incubation of 1 hr, and increased the level of cAMP significantly. The effects of isoprenaline on the contractile force and on the level of cAMP were considerably enhanced by papaverine: the content of cAMP was increased by isoprenaline (3×10−7 M) to about 3 times the control value and also its positive inotropic effect was significantly greater than in controls without papaverine. On the other hand, the positive inotropic effect of methoxamine (10−4 M) was not affected by papaverine (10−5 M). Further-more, in the papillary muscle treated with papaverine the level of cAMP was significantly reduced by methoxamine: the papaverine-induced increase of cAMP was abolished by methoxamine. 4. The present results are compatible with the hypothesis that cAMP is involved as a mediator in the positive inotropic effect induced by β-adrenoceptor stimulation, and indicate further that the stimulation of α-adrenoceptors evokes its positive inotropic effect through a mechanism other than that elicited by β-adrenoceptor stimulation, i.e., independent of cAMP.
    Materialart: Digitale Medien
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  • 4
    ISSN: 1432-1912
    Schlagwort(e): α-Adenoceptors ; β-Adrenoceptors ; Phenylephrine ; cAMP ; Papaverine ; Rabbit papillary muscle
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The time course of changes of the level of 3′,5′-cyclic AMP (cAMP) and of the tension developed under stimulation of α- and β-adrenoceptors by phenylephrine was investigated in the isolated rabbit papillary muscle. Furthermore the doseresponse relationships for increases of cAMP and of developed tension elicited by phenylephrine were determined. 1. A submaximally effective concentration of phenylephrine (10−5 M) increased significantly the level of cAMP of the papillary muscle at 15 and 30 s by 45 and 36%, respectively; the level of cAMP returned to the control value at 60 s after the administration. The developed tension increased significantly not before 45 s and reached its maximal level at 180 s. 2. When α-adrenoceptors were blocked by phentolamine (10−6 M), the positive inotropic effect of phenylephrine was decreased significantly but the increase of cAMP induced by phenylephrine was not reduced. In the presence of phentolamine the increase of cAMP induced by phenylephrine lasted longer than in the control experiments. 3. The effects of phenylephrine (10−5 M) both on the level of cAMP and the developed tension mediated via stimulation of β-adrenoceptors in the presence of phentolamine were enhanced by the phosphodiesterase inhibitor papaverine throughout the course of responses. 4. Phenylephrine produced an increase in developed tension as well as in cAMP. The corresponding dose-response curves run parallel to each other but differed by about 1.5 log units whereby the developed tension was evoked by lower concentrations. Phentolamine (10−6 M) shifted the curve for the positive inotropic action by about 1.5 log units but did not affect that for increase in cAMP. Therefore, in the presence of the α-adrenolytic drug phentolamine the difference between both curves became smaller so that both curves were superimposed. Papaverine (10−5 M) shifted the whole curve for cAMP upwards and enhanced the maximal contractile response to phenylephrine mediated by stimulation of β-adrenoceptors. 5. The present results indicate that the positive inotropic action of phenylephrine in lower concentrations (〈10−5 M) induced by stimulation of α-adrenoceptors is independent of the level of cAMP. The positive inotropic action of the higher concentrations of phenylephrine induced via stimulation of β-adrenoceptors was preceded by an accumulation of cAMP; the inhibition of the cAMP phosphodiesterase activity by papaverine enhanced the actions of phenylephrine both on the level of cAMP and on the contractile force.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 308 (1979), S. 19-23 
    ISSN: 1432-1912
    Schlagwort(e): Dobutamine ; Isoprenaline ; Terbutaline ; Guinea-pig atrium ; Guinea-pig trachea
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Experiments with the dopamine-congener dobutamine were performed on isolated, spontaneously beating right atria as well as on electrically driven left atria of guinea pigs (2 and 3 Hz). Furthermore, its relaxant effect on the tracheal chain was investigated. 1. On right atria dobutamine caused a positive chronotropic effect, the corresponding pD2-value was by 1.75 log units lower than that determined for isoprenaline. The intrinsic activity (isoprenaline=1) was 0.79 for the increase in rate. The pA2-value characterizing the antagonism between metoprolol and dobutamine or isoprenaline for the positive chronotropic effect were comparable indicating that the effects are mediated by the same type of β-adrenoceptor. 2. On the left atrium driven at 2 Hz the pD2-value for the positive inotropic effects of dobutamine and isoprenaline was by 1.82 log units lower for dobutamine than for isoprenaline. The intrinsic activity of dobutamine amounted to 0.62 (isoprenaline=1.0). The pA2-values of metoprolol, on the other hand, did not differ significantly in the presence of either dobutamine or isoprenaline. 3. Since the right atria developed a spontaneous rate of about 3 Hz, left atria were also driven at 3 Hz. The pD2-values of dobutamine under these conditions were 6.05 for the positive chronotropic effect obtained on right atria and 6.07 for the positive inotropic effect obtained on left atria, also the pA2-values determined for metoprolol showed no significant differences. 4. Dobutamine completely relaxed the guinea-pig tracheal chain preparation, its intrinsic activity was identical with that of isoprenaline. The pD2-value amounted to 5.38, that determined for isoprenaline was 7.86. The corresponding pA2-values for metoprolol did not differ from each other: in the presence of dobutamine it amounted to 6.55, while for isoprenaline it was 6.50. 5. By stimulation of cardiac β1-adrenoreceptors dobutamine causes — like isoprenaline — positive inotropic and chronotropic effects of comparable degree. The tracheal β2-adrenoreceptors are also stimulated by dobutamine; the pD2-value for tracheal relaxation was by about 0.69 log units lower than that for cardiostimulation.
    Materialart: Digitale Medien
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  • 6
    ISSN: 1432-1912
    Schlagwort(e): Rabbit papillary muscle ; Ca2+-dependent action potential ; α- + β-Adrenoceptors ; Positive inotropic effect
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The influence of sympathomimetic α- and β-agonists on calcium-dependent slow action potential (SAP) and force of contraction were analyzed in the partially depolarized rabbit papillary muscle. 1. The effects of phenylephrine (3×10−6 mol/l) on SAP were compared with those of isoprenaline (5×10−8 mol/l) since the contractions that could be elicited at these concentrations were of similar amplitude. The maximum rate of rise (V max) of the slow action potential, which was taken to reflect the slow calcium inward current (Isi), was evidently smaller when elicited by phenylephrine than by isoprenaline. 2. V max of SAP induced by phenylephrine (3×10−6 mol/l) or isoprenaline (5×10−8 mol/l) was significantly increased in either case by additional application of isoprenaline. The positive inotropic effect induced by additional isoprenaline was associated with an increase in the rate of force development. 3. V max of SAP evoked by isoprenaline (5×10−8 mol/l) remained unchanged by additional application of phenylephrine (3×10−6 mol/l) whereas the duration of SAP was significantly prolonged. Additional phenylephrine markedly increased the time to peak force but left the rate of force development unchanged. These effects of phenylephrine on slow action potential and force of contraction were completely blocked by prazosin (10−8 mol/l). 4. The duration of SAP induced by dopamine was shortened by prazosin (10−8 mol/l) without alteration of V max, whereas force of contraction was reduced. 5. For further analysis of the mechanisms responsible for the prolongation of SAP by the α-mimetic effect of phenylephrine, additional experiments have been performed. In normal Tyrode solution containing MnCl2 (10 mmol/l), phenylephrine (3×10−6 mol/l) prolonged the duration of action potential without reestablishing force development. Prazosin (10−8 mol/l) completely antagonized this effect of phenylephrine. 6. These findings indicate that an increase in the slow calcium inward current induced by α-stimulation is much smaller than that induced by β-stimulation. The prolongation of the action potential evoked by α-stimulation seems to be induced by a suppression of the time-dependent outward current. This current may play an important role in the α-adrenoceptor-mediated positive inotropic effect.
    Materialart: Digitale Medien
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