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

2013, Naunyn-Schmiedeberg's Archives of Pharmacology

We have recently reported that quinpirole (a D 2like receptor agonist) inhibits the vasopressor sympathetic outflow in pithed rats via sympatho-inhibitory D 2 -like receptors. Since D 2 -like receptors consist of D 2 , D 3 and D 4 receptor subtypes, this study investigated whether these subtypes are involved in the above quinpirole-induced sympathoinhibition by using antagonists of these receptor subtypes. One hundred fifty-six male Wistar rats were pithed and prepared for preganglionic spinal (T 7 -T 9 ) 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 (D 2 ), nafadotride or SB-277011-A (both D 3 ) as well as L-745,870 (D 4 ). 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.