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The role of dopamine D 2 , but not D 3 or D 4 , receptor subtypes, in quinpirole‐induced inhibition of the cardioaccelerator sympathetic outflow in pithed rats
Author(s) -
AltamiranoEspinoza A H,
GonzálezHernández A,
ManriqueMaldonado G,
MarichalCancino B A,
RuizSalinas I,
Villalón C M
Publication year - 2013
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12358
Subject(s) - quinpirole , endocrinology , medicine , chemistry , agonist , stimulation , receptor , dopamine receptor , antagonist , receptor antagonist
Background and Purpose Quinpirole (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 Approach One hundred fourteen male W istar 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 Results 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 ( D 3 ; 100–300 μg kg −1 ) or L‐745,870 ( D 4 ; 30–100 μg kg −1 ); and (ii) markedly blocked and abolished by, respectively, 100 and 300 μg kg −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 Implications The cardiac sympathoinhibition induced by 3 μg kg −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.