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

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 (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 (alpha(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 (alpha(2A)), partially antagonized by MK912 (alpha(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 alpha(2A)/alpha(2C)-adrenoceptors, D(2)-like receptors and, to a lesser extent, by 5-HT(1B/1D) receptors.