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...