Pharmacological Evidence That Dopamine Inhibits the Cardioaccelerator Sympathetic Outflow via D2-Like Receptors in Pithed Rats

Abstract

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.

Pharmacological evidence that 5-HT1A/1B/1D, α2-adrenoceptors and D2-like receptors mediate ergotamine-induced inhibition of the vasopressor sympathetic outflow in pithed rats

“…1). It must be emphasised that the doses used of the above antagonists were high enough to block their respective receptors on the sympathetic nerves (Alcántara- Vázquez et al, 2013;Cobos-Puc et al, 2009;Manrique-Maldonado et al, 2011;Villalón et al, 1998;Villamil-Hernández et al, 2013b) by which display affinity (Table 1).…”

“…Admittedly further experiments using selective antagonists for each α 2 subtype, which fall beyond the scope of the present investigation, will be required to identify the α 2 subtype involved. Finally, the fact that 300 mg/kg raclopride, a D 2 -like receptor antagonist (Alcántara-Vázquez et al, 2013), produced only a partial blockade of the vasopressor sympatho-inhibition to ergotamine (Fig. 5(F)) at 3 Hz, we decided to analyse the effect of 1000 mg/kg, which abolished the vasopressor sympatho-inhibition to quinpirole (Manrique-Maldonado et al, 2011), a D 2 -like agonist.…”