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Organic and inorganic calcium antagonists reduce vasoconstriction in vivo mediated by postsynaptic α 2-Adrenoceptors

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Summary

The influence of various calcium antagonists and divalent metal cations on the pressor responses induced by the selective α 1-adrenoceptor agonist methoxamine and the selective α 2-adrenoceptor stimulating agent B-HT 920 (2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo-[4,5-d]-azepine) was studied in pithed rats.

  1. 1.

    The calcium antagonists verapamil, D 600 and nifedipine, when given intraarterially (i.a.) in doses up to 1 mg/kg did not influence the pressor effects of methoxamine. Only higher amounts of these calcium antagonistic drugs (1–3 mg/kg i.a.) somewhat reduced this pressor response.

  2. 2.

    The vasoconstriction due to B-HT 920, as reflected by the increase in diastolic pressure, was markedly inhibited by verapamil, D 600 and nifedipine in a dose-dependent manner. In low doses a parallel displacement to the right was observed, whereas in higher amounts the shift was non-parallel.

  3. 3.

    The divalent cations Mn2+, Ni2+ and Co2+ (0.05–0.15 mmol/kg i.a.) hardly affected the pressor effect of methoxamine, whereas B-HT 920-induced vasoconstriction was highly sensitive to these metal ions. La3+ and Mg2+ were ineffective.

  4. 4.

    The calcium antagonists verapamil, D 600 and nifedipine displayed only minor affinities for [3H]prazosin (α 1) as well as [3H]clonidine (α 2) binding sites of rat brain membranes.

  5. 5.

    It is concluded that an influx of extracellular Ca2+ is necessary for the vasoconstriction in vivo initiated by stimulation of vascular postsynaptic α 2-adrenoceptors. On the other hand, vasopressor responses to α 1-adrenoceptor stimulation are not directly dependent on a transmembrane influx of calcium ions.

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Authors and Affiliations

  1. Department of Pharmacy, Division of Pharmacotherapy, University of Amsterdam, Plantage Muidergracht 24, NL-1018 TV, Amsterdam, The Netherlands

    J. C. A. van Meel, A. de Jonge, H. O. Kalkman, B. Wilffert, P. B. M. W. M. Timmermans & P. A. van Zwieten

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  1. J. C. A. van Meel
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  2. A. de Jonge
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  3. H. O. Kalkman
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  4. B. Wilffert
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  5. P. B. M. W. M. Timmermans
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  6. P. A. van Zwieten
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van Meel, J.C.A., de Jonge, A., Kalkman, H.O. et al. Organic and inorganic calcium antagonists reduce vasoconstriction in vivo mediated by postsynaptic α 2-Adrenoceptors. Naunyn-Schmiedeberg's Arch. Pharmacol. 316, 288–293 (1981). https://doi.org/10.1007/BF00501359

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  • DOI: https://doi.org/10.1007/BF00501359

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