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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 265 (1969), S. 170-186 
    ISSN: 1432-1912
    Keywords: Angiotensin ; Noradrenaline Release ; Isolated Rabbit Heart ; Sympathetic Nerves ; Angiotensin ; Noradrenalinabgabe ; Isoliertes Kaninchen herz ; Sympathische Nerven
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The influence of angiotensin on the isolated rabbit heart perfused at constant pressure or constant flow was investigated at rest and during electrical stimulation of the postganglionic sympathetic nerves. 2. In low concentrations (32–100ng/min or 1.4–5.3 ng/ml) angiotensin had considerable positive inotropic effects, while its chronotropic effects were weak and variable. High concentrations decreased the rate of beat, and an increase in the height of contraction was preceded by a transient phase of inhibition. In hearts perfused at constant pressure, angiotensin diminished coronary flow. The positive inotropic effect of angiotensin was not accompanied by the appearance of increased amounts of noradrenaline in the venous effluent. 3. Angiotensin caused a dose-dependent increase in the output of noradrenaline induced by sympathetic nerve stimulation. The peptide was most potent in hearts perfused at constant flow; the threshhold dose of angiotensin for this procedure was 3.2 ng/min (128 pg/ml), and maximal effects (i.e., an increase by 81%) were observed with 32 ng/min (1.28 ng/ml). Doses about three times higher were required to obtain similar effects in hearts perfused at constant pressure. The reduction of coronary flow as seen under these conditions may be responsible for the weaker effect of angiotensin. Continuous infusion increased the output of noradrenaline during several successive stimulation periods. 4. In most cases, the increase in output of noradrenaline induced by angiotensin did not lead to an increase in the response of the pacemaker or of the myocardium to sympathetic stimulation. Only in hearts perfused at constant flow during infusion of 32 ng/min of angiotensin the positive inotropic effect of sympathetic stimulation was significantly augmented. 5. The results indicate that angiotensin may modulate the activity of the autonomic nervous system by influencing peripheral sympathetic nerves.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 268 (1971), S. 102-113 
    ISSN: 1432-1912
    Keywords: Β-Receptor Blocking Drugs ; Isolated Rabbit Heart ; Noradrenaline Output ; Noradrenaline Uptake ; Β-Adrenolytika ; Isoliertes Kaninchenherz ; Noradrenalinabgabe ; Noradrenalinaufnahme
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using isolated rabbit hearts with sympathetic nerve supply we have studied the influence of LB 46, (−)- and (+)-INPEA, (−) and (+)-propranolol on the output of noradrenaline evoked by electrical stimulation of the sympathetic nerves. 1. LB 46, (−)-INPEA and the optical isomers of propranolol, drugs with differentΒ-receptor blocking potency, increase the noradrenaline output induced by electrical nerve stimulation. 2. Likewise, (+)-INPEA, which lacksΒ-receptor blocking activity, enhances the noradrenaline output to the same extent as theΒ-receptor blocking (−)-isomer. 3. High concentrations of both optical isomers of propranolol have a cardiodepressant action; they do not further augment the noradrenaline output but inhibit it. 4. Additional experiments with the optical isomers of INPEA show an inhibition by these drugs of the uptake of noradrenaline by the rabbit heart. The latter observation favours the hypothesis that all drugs tested increase the noradrenaline output by an inhibition of re-uptake. The ability of these drugs to inhibit the noradrenaline re-uptake is independent of theirΒ-receptor blocking action.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1912
    Keywords: Papaverine ; Isoprenaline ; cAMP ; Contractility ; Frequency of stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1912
    Keywords: α-and β-Adrenoceptors ; Methoxamine ; Isoprenaline ; cAMP ; Papaverine ; Rabbit Papillary Muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 308 (1979), S. 19-23 
    ISSN: 1432-1912
    Keywords: Dobutamine ; Isoprenaline ; Terbutaline ; Guinea-pig atrium ; Guinea-pig trachea
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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