The role of dopamine D2, but not D3 or D4, receptor subtypes, in quinpirole-induced inhibition of the cardioaccelerator sympathetic outflow in pithed rats.

Abstract

Quinpirole (a dopamine D2-like receptor agonist) inhibits the cardioaccelerator sympathetic outflow in pithed rats by sympathoinhibitory D2-like receptors. The present study was designed to identify pharmacologically the specific D2-like receptor subtypes (i.e. D2 , D3 and D4) involved in this sympathoinhibition by quinpirole. One hundred fourteen male Wistar rats were pithed, artificially ventilated with room air and prepared for either preganglionic spinal (C7-T1) stimulation of the cardioaccelerator sympathetic outflow (n = 102) or i.v. bolus injections of exogenous noradrenaline (n = 12). This approach resulted in frequency-dependent and dose-dependent tachycardic responses, respectively, as previously reported by our group. I.v. continuous infusions of quinpirole (0.1-10 μg kg(-1) min(-1)), but not of saline (0.02 mL min(-1)), dose-dependently inhibited the sympathetically induced tachycardic responses. Moreover, the cardiac sympathoinhibition induced by 3 μg kg(-1) min(-1) quinpirole (which failed to affect the tachycardic responses to i.v. noradrenaline) was: (i) unchanged after i.v. injections of the antagonists SB-277011-A (D3 ; 100-300 μg kg(-1)) or L-745,870 (D4 ; 30-100 μg kg(-1)); and (ii) markedly blocked and abolished by, respectively, 100 and 300 μg kg(-1) of the D2 preferring receptor subtype antagonist L-741,626. These doses of antagonists, which did not affect per se the sympathetically induced tachycardic responses, were high enough to completely block their respective receptors. The cardiac sympathoinhibition induced by 3 μg kg(-1) min(-1) quinpirole involves the dopamine D2 receptor subtype, with no evidence for the involvement of the D3 or D4 subtypes. This provides new evidence for understanding the modulation of the cardioaccelerator sympathetic outflow.