Organic and inorganic calcium antagonists reduce vasoconstriction in vivo mediated by postsynaptic α2-Adrenoceptors

  • J. C. A. van Meel
  • A. de Jonge
  • H. O. Kalkman
  • B. Wilffert
  • P. B. M. W. M. Timmermans
  • P. A. van Zwieten
Article
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Summary

The influence of various calcium antagonists and divalent metal cations on the pressor responses induced by the selective α1-adrenoceptor agonist methoxamine and the selective α2-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 (α1) as well as [3H]clonidine (α2) 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 α2-adrenoceptors. On the other hand, vasopressor responses to α1-adrenoceptor stimulation are not directly dependent on a transmembrane influx of calcium ions.

     

Key words

Postsynaptic α1- α2-adrenoceptors Methoxamine B-HT 920 Calcium antagonists Divalent metal ions Calcium ions Vasoconstriction 
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Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • J. C. A. van Meel
    • 1
  • A. de Jonge
    • 1
  • H. O. Kalkman
    • 1
  • B. Wilffert
    • 1
  • P. B. M. W. M. Timmermans
    • 1
  • P. A. van Zwieten
    • 1
  1. 1.Department of Pharmacy, Division of PharmacotherapyUniversity of AmsterdamAmsterdamThe Netherlands

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