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

Background and PurposeQuinpirole (a dopamine D-2-like receptor agonist) inhibits the cardioaccelerator sympathetic outflow in pithed rats by sympathoinhibitory D-2-like receptors. The present study was designed to identify pharmacologically the specific D-2-like receptor subtypes (i.e. D-2, D-3 and D-4) involved in this sympathoinhibition by quinpirole. Experimental ApproachOne hundred fourteen male Wistar rats were pithed, artificially ventilated with room air and prepared for either preganglionic spinal (C-7-T-1) 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. Key ResultsI.v. continuous infusions of quinpirole (0.1-10gkg(-1)min(-1)), but not of saline (0.02mLmin(-1)), dose-dependently inhibited the sympathetically induced tachycardic responses. Moreover, the cardiac sympathoinhibition induced by 3gkg(-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 (D-3; 100-300gkg(-1)) or L-745,870 (D-4; 30-100gkg(-1)); and (ii) markedly blocked and abolished by, respectively, 100 and 300gkg(-1) of the D-2 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. Conclusions and ImplicationsThe cardiac sympathoinhibition induced by 3gkg(-1)min(-1) quinpirole involves the dopamine D-2 receptor subtype, with no evidence for the involvement of the D-3 or D-4 subtypes. This provides new evidence for understanding the modulation of the cardioaccelerator sympathetic outflow.