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Pharmacological characterization of ergotamine-induced inhibition of the cardioaccelerator sympathetic outflow in pithed rats

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Abstract

Ergotamine inhibits the sympathetically-induced tachycardia in pithed rats. The present study identified the pharmacological profile of this response. Male Wistar rats were pithed and prepared to stimulate the preganglionic (C7–T1) cardiac sympathetic outflow. Intravenous continuous infusions of ergotamine dose-dependently inhibited the tachycardic responses to sympathetic stimulation, but not those to exogenous noradrenaline. Using several antagonists, the sympatho-inhibition to ergotamine was: (1) partially blocked by rauwolscine (α2), haloperidol (D1/2-like) or rauwolscine plus GR127935 (5-HT1B/1D); (2) abolished by rauwolscine plus haloperidol; and (3) unaffected by either saline or GR127935. In animals systematically pretreated with haloperidol, this sympatho-inhibition was: (1) unaffected by BRL44408 (α2A), partially antagonized by MK912 (α2C); and (3) abolished by BRL44408 plus MK912. These antagonists failed to modify the sympathetically induced tachycardic responses per se. Thus, the cardiac sympatho-inhibition by ergotamine may be mainly mediated by α2A/α2C-adrenoceptors, D2-like receptors and, to a lesser extent, by 5-HT1B/1D receptors.

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Acknowledgements

The technical assistance of Mr. Arturo Contreras is gratefully acknowledged. We also thank to CONACyT (México) for their financial support.

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Authors and Affiliations

  1. Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, C.P. 14330, México D.F., México

    Luis E. Cobos-Puc, Carlos M. Villalón, Araceli Sánchez-López, Martha B. Ramírez-Rosas, Jair Lozano-Cuenca & David Centurión

  2. Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195, Berlin (Dahlem), Germany

    Heinz H. Pertz & Tilo Görnemann

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  1. Luis E. Cobos-Puc
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  2. Carlos M. Villalón
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  3. Araceli Sánchez-López
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  4. Martha B. Ramírez-Rosas
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  7. Tilo Görnemann
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  8. David Centurión
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Correspondence to David Centurión.

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Cobos-Puc, L.E., Villalón, C.M., Sánchez-López, A. et al. Pharmacological characterization of ergotamine-induced inhibition of the cardioaccelerator sympathetic outflow in pithed rats. Naunyn-Schmied Arch Pharmacol 379, 137–148 (2009). https://doi.org/10.1007/s00210-008-0339-y

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  • DOI: https://doi.org/10.1007/s00210-008-0339-y

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