Predominant role of the dopamine D₃ receptor subtype for mediating the quinpirole-induced inhibition of the vasopressor sympathetic outflow in pithed rats

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.