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This study investigated in pithed rats whether dopamine can inhibit the sympathetic vasopressor outflow and analysed the pharmacological profile of the receptors involved. Male Wistar pithed rats were pre-treated with intravenous (i.v.) bolus injections of gallamine (25 mg ⁄ kg) and desipramine (50 lg ⁄ kg). The vasopressor responses to electrical stimulation of the sympathetic vasopressor outflow (0.03-3 Hz; 50 V and 2 msec.) were analysed before and during i.v. continuous infusions of the agonists dopamine (endogenous ligand), SKF-38393 (D 1 -like) or quinpirole (D 2 -like). If inhibition was produced by any agonist, then its capability to inhibit the vasopressor responses to i.v. bolus injections of exogenous noradrenaline (0.03-3 lg ⁄ kg) was also investigated. Dopamine (3-100 lg ⁄ kg min.) inhibited the vasopressor responses to both electrical stimulation and noradrenaline. In contrast, SKF-38393 (10-100 lg ⁄ kg min.) failed to inhibit the vasopressor responses to electrical stimulation; whereas quinpirole (0.1-30 lg ⁄ kg min.) inhibited the vasopressor responses to electrical stimulation but not those to noradrenaline. The sympatho-inhibition by quinpirole (1 lg ⁄ kg min.) remained unaltered after i. Dopamine produces complex cardiovascular effects by interacting with a-and b-adrenoceptors and ⁄ or dopamine receptors [4,[6][7][8]. At the vascular level, D 1 -like receptors are mainly located on smooth muscle (mediating direct vasodilatation), whereas D 2 -like receptors are located on perivascular sympathetic nerves (mediating sympatho-inhibition) [4,9].Many studies have described the sympatho-inhibitory effects of dopamine on isolated blood vessels and other tissues [3], but no study has reported this effect on the systemic vasculature. For example, when analysing the sympathetic vasopressor outflow in pithed rats: (i) Hietala et al. [10] proposed that dopamine receptors may produce sympathoinhibition, but no selective antagonists were used; and (ii) Fernµndez et al. Materials and MethodsGeneral methods. All animal protocols were approved by our Institutional Ethics Committee, in accordance with the guide for the Care and Use of Laboratory Animals in the USA. Experiments were carried out in 120 male Wistar normotensive rats (250-280 g). After anaesthesia with diethyl ether and cannulation of the trachea, the rats were pithed by inserting a stainless steel rod as reported earlier [12]. Then, the animals were artificially ventilated with room air using a model 7025 Ugo Basile pump (56 strokes ⁄ min.; stroke volume: 20 ml ⁄ kg), as previously established [13]. After bilateral vagotomy, catheters were placed in: (i) the left and right femoral veins, for the infusions of agonists and i.v. bolus injections of antagonists, respectively; and (ii) the left carotid artery, connected to a Grass pressure transducer (P23XL), for recording blood pressure. Both heart rate (measured with a 7P4F tachograph) and blood pressure were recorded simultaneously by a model 7D Grass polygraph (Grass Instrument Co., Quin...

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Abstract. It has been suggested that N,N-di-n-propyl-dopamine (dopamine analogue) decreased heart rate in rats through stimulation of dopamine receptors. Nevertheless, the role of prejunctional dopamine D 1/2 -like receptors or even a 2 -adrenoceptors to mediate cardiac sympatho-inhibition induced by dopamine remains unclear. Hence, this study identified the pharmacological profile of the cardiac sympatho-inhibition to dopamine in pithed rats. Male Wistar rats were pithed and prepared to stimulate the cardiac sympathetic outflow or to receive i.v. bolus of exogenous noradrenaline. I.v. continuous infusions of dopamine (endogenous ligand) or quinpirole (D 2 -like agonist) dose-dependently inhibited the tachycardic responses to sympathetic stimulation, but not those to exogenous noradrenaline. In contrast, SKF-38393 (100 mg/kg•min, D 1 -like agonist) failed to modify both of these responses. The sympatho-inhibition to dopamine (1.8 mg/kg•min) or quinpirole (100 mg/kg•min): i) remained unaltered after saline or the antagonists SCH-23390 (D 1 -like, 300 mg/kg) and rauwolscine (a 2 -adrenoceptors, 300 mg/kg); and ii) was significantly antagonized by raclopride (D 2 -like, 300 mg/kg). These antagonists, at the above doses, failed to modify the sympatheticallyinduced tachycardic responses. The above results suggest that the inhibition of the cardiac sympathetic outflow to dopamine and quinpirole is primarily mediated by prejunctional D 2 -like receptors but not D 1 -like receptors or a 2 -adrenoceptors.