Predominant role of the dopamine D3 receptor subtype for mediating the quinpirole-induced inhibition of the vasopressor sympathetic outflow in pithed rats
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Abstract
We have recently reported that quinpirole (a D2-like receptor agonist) inhibits the vasopressor sympathetic outflow in pithed rats via sympatho-inhibitory D2-like receptors. Since D2-like receptors consist of D2, D3 and D4 receptor subtypes, this study investigated whether these subtypes are involved in the above quinpirole-induced sympatho-inhibition by using antagonists of these receptor subtypes. One hundred fifty-six male Wistar rats were pithed and prepared for preganglionic spinal (T7–T9) stimulation of the vasopressor sympathetic outflow. This approach resulted in frequency-dependent vasopressor responses which were analysed before and during i.v. continuous infusions of either saline (0.02 ml/min) or quinpirole (1 μg/kg.min) in animals receiving i.v. bolus injections of vehicle [saline or dimethyl sulfoxide (DMSO)] or the antagonists L-741,626 (D2), nafadotride or SB-277011-A (both D3) as well as L-745,870 (D4). Quinpirole inhibited the sympathetically-induced vasopressor responses. This sympatho-inhibition was (a) unaltered after 1 ml/kg saline, DMSO or 100 and 300 μg/kg L-741,626; (b) markedly blocked and abolished by, respectively, 30 and 100 μg/kg nafadotride or 100 and 300 μg/kg SB-277011-A and (c) slightly blocked after 30 and 100 μg/kg L-745,870, but 300 μg/kg L-745,870 produced no blockade whatsoever. Except for 300 μg/kg L-741,626 or 300 μg/kg L-745,870, the doses of the above compounds failed to modify per se the sympathetic vasopressor responses. The inhibition of the vasopressor sympathetic outflow induced by 1 μg/kg.min quinpirole in pithed rats is predominantly mediated by dopamine D3 and, to a lesser extent, by D4 receptor subtypes, with no evidence for the involvement of the D2 subtype.
Keywords
L-741,626 L-745,870 Nafadotride SB-277011-A Quinpirole Vasopressor sympathetic outflowNotes
Acknowledgments
The authors would like to thank Mr. Mauricio Villasana for his skilful technical assistance. The present study was financially supported by the Consejo Nacional de Ciencia y Tecnología (CONACyT, project no. 60789; México DF).
Conflict of interest
The authors declare that they have no conflict of interest.
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