Effects of quinpirole on autonomic nervous control of heart rate in rats

Abstract

The effects of quinpirole, a specific dopamine DA2 receptor agonist, on autonomic nervous control of heart rate, were studied in normotensive pithed rats, by analysing its action on the tachycardia and bradycardia evoked by electrical stimulation of the cardioaccelerator (10 V; 1 ms; 0.5, 1, 3, 6 Hz) and vagus (10 V; 1 ms; 3, 6, 9 Hz) nerves respectively. Quinpirole (10-50-100 micrograms kg-1 iv) reduced the cardioacceleration elicited by electrical stimulation but not that by noradrenaline (3 micrograms kg-1 iv). The effect on electrical stimulation was blocked by domperidone (0.5 mg kg-1 iv) but not by SCH 23390 (0.2 mg kg-1 iv) or idazoxan (0.3 mg kg-1 iv). At 1, 5, 10, 30 micrograms kg-1 iv, quinpirole decreased vagal but not acetylcholine-induced bradycardia. The effect on electrical stimulation was inhibited by domperidone (0.5 mg kg-1 iv) but not by SCH 23390 (0.2 mg kg-1 iv), prazosin (0.1 mg kg-1 iv) or idazoxan (0.3 mg kg-1 iv). The data point to the presence of presynaptic and/or ganglionic dopamine receptors in the sympathetic and parasympathetic innervation of the rat heart, where stimulation inhibits the release of neuromediators.

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

“…6f) or rauwolscine (Fig. 6h) reinforces the view that D 2 -like, but not D 1 -like, receptors are involved in cardiac-sympatho-inhibition as previously shown (11).…”

“…In this respect, it should be pointed out that the responses evaluated by Manrique-Maldonado (32) (vasopressor responses) were completely different and the difference may be due to variation in the expression/ functionality of the dopamine receptors. Hence, we used a higher dose (100 mg/kg•min) that elicited a marked sympatho-inhibition without affecting the tachycardic responses to noradrenaline, suggesting that D 2 -like receptors are involved as previously shown (11). It is noteworthy that the sympatho-inhibition elicited by dopamine and quinpirole was not because of tachyphylaxis as the sympathetic responses remained unchanged in animals receiving saline (Fig.…”

“…receptors (10); and ii) quinpirole, a D 2 -like agonist, produced cardiac sympatho-inhibition (11). Despite the above findings, unfortunately, the following has not been determined: i) the effect of dopamine, the endogenous ligand, on the electrically-induced tachycardic responses and the pharmacological nature of the receptors involved; ii) the effect of selective D 1/2 -like receptor and a 2 -adrenoceptor antagonists; iii) the effect of D 1 -like receptor agonist on the sympathetically-induced tachycardia; and iv) the prejunctional/postjunctional nature of the inhibition of dopamine by using exogenous noradrenaline.…”

Cardiovascular responses to intrathecal dopamine receptor agonists in conscious DOCA‐salt hypertensive rats

“…) or in animals which had been subjected to either peripheral blockade by i.v. domperidone (500 pg/kg) [23,24,[31][32][33][34][35], or spinal blockade by i.t. domperidone (40 pg/rat at T2-T4).…”

Hypotensive action of bromocriptine in the DOCA‐salt hypertensive rat: Contribution of spinal dopamine receptors

“…These experiments employed the dopamine D1 receptor antagonist, domperidone, which does not cross the bloodbrain barrier. Therefore, the time course of changes in MAP induced by iv bromocriptine ( 150 ,ug/kg) was assessed in animals pretreated with vehicle (iv or it; first group) or in animals which had been subjected to either peripheral blockade by iv domperidone (500 pg/kg; second group) [ I I , 13, [35][36][37]. spinal blockade by it domperidone (40 pg/rat at T9-Tl(,; third group) [ 14, IS, 301 or combined peripheral and spinal blockade by iv (SO0 ,ug/kg, 10 min before) and it (40 pg/rat at T9-TI,,, 5 min before) domperidone, respectively (fourth group), of dopamine D, receptors.…”