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

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2009-02, Vol.379 (2), p.137-148
• Main Authors: Cobos-Puc, Luis E., Villalón, Carlos M., Sánchez-López, Araceli, Ramírez-Rosas, Martha B., Lozano-Cuenca, Jair, Pertz, Heinz H., Görnemann, Tilo, Centurión, David
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-2 Receptor Antagonists; Adrenergic alpha-Agonists - administration & dosage; Adrenergic alpha-Agonists - pharmacology; Animals; Biomedical and Life Sciences; Biomedicine; Decerebrate State; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Electric Stimulation; Ergotamine - administration & dosage; Ergotamine - pharmacology; Infusions, Intravenous; Male; Neurosciences; Original Article; Pharmacology/Toxicology; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT1B - physiology; Receptor, Serotonin, 5-HT1D - physiology; Receptors, Adrenergic, alpha-2 - physiology; Receptors, Dopamine D2 - physiology; Sympathetic Nervous System - physiopathology; Tachycardia - physiopathology
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/s00210-008-0339-y

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 (C 7 –T 1 ) 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 (α 2 ), haloperidol (D 1/2 -like) or rauwolscine plus GR127935 (5-HT 1B/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 (α 2A ), partially antagonized by MK912 (α 2C ); 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 α 2A /α 2C -adrenoceptors, D 2 -like receptors and, to a lesser extent, by 5-HT 1B/1D receptors.