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  • Articles: DFG German National Licenses  (6)
  • Electronic Resource  (6)
  • α-Adrenoceptors  (4)
  • Papillary muscle  (2)
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  • Articles: DFG German National Licenses  (6)
Material
  • Electronic Resource  (6)
Years
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 302 (1978), S. 235-238 
    ISSN: 1432-1912
    Keywords: Nifedipine ; Verapamil ; Calcium ; Ventricular automaticity ; Papillary muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In isolated, blood-perfused canine papillary muscles intra-arterial injection of calcium-antagonistic coronary vasodilators, nifedipine and verapamil, produced a dose-related decrease in force of contraction. The ventricular rate of about 40 beats/min was not significantly changed by nifedipine even in doses which profoundly decreased the force of contraction. Verapamil changed the ventricular rate in a biphasic manner, but the changes remained as small as about 10% of the basal rate in doses which markedly suppressed the force of contration. Calcium chloride elicited an increase in force of contraction but depressed automaticity. The present results show that in response to nifedipine, verapamil and calcium ions, ventricular automaticity has characteristics different from those of the sinus node.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 287 (1975), S. 61-72 
    ISSN: 1432-1912
    Keywords: α-Adrenoceptors ; Frequency-Force Relationship ; Temperature ; D600 ; Rabbit Papillary Muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary On the isolated rabbit papillary muscle experiments were carried out to determine whether the positive inotropic effects mediated by α- and by β-adrenoceptors are brought about by different mechanisms or not.—For this reason the influence of temperature and the effect of the calcium antagonist D600 on the responses to phenylephrine and to isoprenaline were compared. 1. The maximal inotropic effects of phenylephrine, isoprenaline and calcium were not affected by raising the temperature of the organ bath from 37° to 42°C whereas the basal developed tension of the muscle was significantly decreased. 2. The dose-response curve for phenylephrine was markedly shifted to the right by raising the temperature (ΔpD 2=0.89), while that for isoprenaline was also shifted to the right, but to a lesser extent (ΔpD 2=0.23). 3. In the presence of 1.5 × 10−8M pindolol the shift of the dose-response curve for phenylephrine induced by elevation of temperature was more prominent (ΔpD 2=1.91), whereas phentolamine (3 × 10−6M) inhibited the temperatureinduced shift. 4. The positive inotropic effect of phenylephrine—mediated by α-adrenoceptors under blockade of β-adrenoceptors by 1.5 × 10−8M pindolol—was markedly depressed by D600 (10−7 and 3 × 10−7M): the dose-response curve was shifted to the right and the maximal response was depressed. On the other hand, the positive inotropic effect of isoprenaline—mediated by β-adrenoceptors—was affected to a lesser extent by D600 and the maximal response was not changed. 5. These results indicate that the stimulation of α-adrenoceptors in the rabbit papillary muscle induces a positive inotropic response through a biochemical process different from that caused via β-adrenoceptors, i.e., stimulation of α-adrenoceptors may increase the intracellular calcium level mainly by changing the transmembrane calcium flux.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 287 (1975), S. 377-389 
    ISSN: 1432-1912
    Keywords: α-Adrenoceptors ; Methoxamine ; Naphazoline ; Frequency-force Relationship ; Rabbit Papillary Muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Under the conditions of different stimulation frequencies the inotropic effects of the α-adrenoceptor stimulating agents, methoxamine, naphazoline and oxymetazoline were studied on the isolated rabbit papillary muscle. 1. On the papillary muscle stimulated at 0.5 Hz methoxamine in concentrations from 10−5 to 3×10−4 M caused a significant and dose-dependent positive inotropic effect. At 10−3 M methoxamine decreased the developed tension. With increasing frequency of stimulation (0.5–1–1.5 Hz), the positive inotropic effect became smaller, while the negative inotropic one was more pronounced. The time course of the disappearance of the negative inotropic effect of methoxamine by washout differed from that of the positive inotropic effect: the negative component disappeared within 30 min, whereas the positive one lasted for about 100 min. The positive inotropic effect of noradrenaline (10−6 M), in contrast to that of methoxamine, was not influenced by the frequency under the same conditions of stimulation. Also naphazoline (10−5 M) caused a significant positive inotropic effect on the papillary muscle stimulated at 0.5 Hz, while oxymetazoline induced exclusively a negative inotropic effect. 2. The positive inotropic effect of methoxamine (10−4 M) as well as of naphazoline (10−5 M) evoked at a frequency of 0.5 Hz was abolished by phentolamine (10−6 M). Methoxamine (10−4 M) induced a significant negative inotropic effect in the presence of phentolamine. Phentolamine antagonized the positive inotropic effect of methoxamine in a non-competitive manner: the pD′2-value was 7.76. 3. In the presence of methoxamine (10−4 M) the developed tension in the lower range (0.05–1 Hz) of the frequency-force relationship was enhanced, while that in the higher range (〉1.5 Hz) was decreased. The enhancement was abolished by phentolamine (10−6 M). 4. Papaverine (2×10−5 M) did not affect the positive inotropic effect of methoxamine. 5. The present results show that methoxamine and naphazoline induced a positive inotropic effect via α-adrenoceptors in the ventricular myocardium of the rabbit. These effects were caused only at low, but not at high frequencies of stimulation.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1912
    Keywords: Dopamine ; Contractility ; Papillary muscle ; α- and β-adrenoceptors ; Cyclic AMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the isolated rabbit papillary muscle the effects of dopamine on the contractile force and on the level of 3′,5′-cyclic adenosine monophosphate (cAMP) at different frequencies of stimulation were studied and compared with those of isoprenaline and adrenaline. 1. When the frequency of stimulation was increased from 0.5–2.5 Hz the dose-response curves for the positive inotropic effect of dopamine as well as of isoprenaline were shifted to the left, whereas the maximum of the developed tension reached for both drugs remained unchanged. 2. At a frequency of stimulation of 0.5 Hz pindolol (3×10−8 M) and phentolamine (10−6 M), respectively, did not affect the dose-response curve for dopamine; only the simultaneous administration of pindolol plus phentolamine shifted the dose-response curve to the right. In the presence of cocaine (3×10−5 M) as well as in that of cocaine plus corticosterone (4×10−5 M) the dose-response curve for dopamine was shifted to the right. On the other hand, the upper part of the dose-response curve for adrenaline was shifted to the right by pindolol (3×10−8 M), the lower part by phentolamine (10−6 M) and the whole curve by the application of both antagonists. 3. At a frequency of stimulation of 2.5 Hz neither pindolol (3×10−8 M) nor phetolamine (10−6 M) influenced the dose-response curve for dopamine, whereas the simultaneous administration of both drugs shifted the whole curve to the right. 4. Dopamine (10−4 M) increased significantly the content of the cAMP after 60 s by about 40% (at 0.5 Hz) and 50% (at 1.0 Hz), respectively, but this increase was by far less compared with that obtained by isoprenaline (3×10−7 M). 5. Pindolol (3×10−8 M) completely abolished the increase of the cAMP-content evoked by dopamine (10−4 M), while phentolamine (10−6 M) enhanced the elevation of the cAMP-level to nearly the same extent as isoprenaline (3×10−7 M) did. 6. The increase of the cAMP level induced by adrenaline (10−5 M) was comparable with that caused by isoprenaline (3×10−7 M). While phentolamine (10−6 M) did not influence the adrenaline induced increase of the cAMP content, pindolol completely abolished it. 7. The present results are compatible with the view, that the positive inotropic effect via stimulation of β-adrenoceptors is mediated by cAMP, while that of α-adrenoceptors is not. Furthermore it is concluded, that dopamine produces its positive inotropic effect by a cAMP-dependent direct and/or indirect β-adrenoceptor stimulation as well as by a cAMP-independent direct α-adrenoceptor stimulation to about the same degree.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 341 (1990), S. 206-214 
    ISSN: 1432-1912
    Keywords: Calcium antagonists ; α-Adrenoceptors ; β-Adrenoceptors ; Positive inotropic effect ; Rabbit ventricular myocardium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Experiments were carried out to elucidate the mechanism that the positive inotropic effect mediated by α1-adrenoceptors is more susceptible to organic calcium antagonists than the β-adrenoceptor-mediated effect. Verapamil and diltiazem displaced the specific binding of [3H]prazosin to the membrane fraction derived from the rabbit ventricular myocardium, verapamil being about 70 times more potent than diltiazem. Nifedipine did not displace the binding. While these compounds suppressed the positive inotropic effect mediated via αl-adrenoceptors in α1- concentration-dependent manner, there was no correlation between the potency of the compounds to displace the [3H]prazosin binding and to inhibit the α-mediated positive inotropic effect. The relative potency of three calcium antagonists to decrease the basal force of contraction and the al-mediated effect (of the same extent as compared to basal force of contraction) was consistent to each other. The positive inotropic effect mediated by β-adrenoceptors was inhibited much less, and was enhanced by low concentrations of organic calcium antagonists. The differential action of calcium antagonists on the α- and β-mediated positive inotropic effect was mimicked by lowering the extracellular calcium concentration to 1/2, 1/4 and 1/8 of that in normal Krebs-Henseleit solution (2.5 mmol/l). These results indicate that the α1-adrenoceptor blocking activity does not play an essential role for the preferential inhibition of α-mediated positive inotropic effect by organic calcium antagonists. Difference in the subcellular mechanism involved in mobilization of intracellular Ca2+ subsequent to α1-and β-adrenoceptor activation may be responsible for the differential inhibitory action of calcium antagonists in the rabbit heart.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 339 (1989), S. 362-366 
    ISSN: 1432-1912
    Keywords: α-Adrenoceptors ; β-Adrenoceptors ; Positive isotropic effect ; Phenylephrine ; Ferret ventricular myocardium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary [3H]prazosin bound to the membrane fraction derived from the ferret ventricular muscle with high affinity in a saturable manner (K d = 0.25 nmol/l and B max = 27 fmol/mg protein in the right ventricle). [3H]CGP-12177, a β-adrenoceptor ligand, bound to the membrane fraction with a K d value of 0.29 nmol/l and a B max of 42 fmol/mg protein. In the isolated ferret papillary muscle driven at 1 Hz at 37°C, phenylephrine elicited a concentration-dependent positive intropic effect. The maximal effect of phenylephrine was comparable to that of isoprenaline. Prazosin (0.3 μol/l) shifted the concentration-response curve for phenylephrine slightly but significantly to the right, the maximal response being unaffected. In contrast, bupranolol (0.3 gmol/l) shifted the curve for phenylephrine markedly downwards: the maximal response was depressed significantly to 40% and the curve became less steep. In the presence of prazosin and bupranolol the curve was shifted to the right, being essentially parallel to the control curve. These results indicate that in the ferret ventricular myocardium both α- and β-adrenoceptors mediate the positive inotropic effect of phenylephrine. The extent of contribution of the two classes of adrenoceptor is quite different from that in other mammalian species. In the ferret heart, β-adrenoceptors predominate over α-adrenoceptors in mediating the positive inotropic effect of phenylephrine, although the number of β-adrenoceptors is not especially high when compared with other species.
    Type of Medium: Electronic Resource
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