Blockade of Spinal Dopamine D₂ Receptors Enhances the Pressor Effect of Intravenous Quinpirole in Normotensive, Conscious Rats

Abstract

The present investigation was undertaken to examine whether in conscious intact rats blockade of spinal dopamine D 2 receptors enhances the pressor effect of intravenous quinpirole. In saline-pretreated rats, intravenous quinpirole (1 mg/kg) induced a significant pressor effect, which reached a maximum (17.71∫0.60 mmHg) within the first min. after injection. Pretreatment with intravenous (0.5 mg/kg) or intrathecal (40 mg/rat at T 9 -T 10 ) domperidone, a dopamine D 2 receptor antagonist that does not cross the blood-brain barrier, significantly enhanced the maximal pressor response to quinpirole (25.60∫1.52 and 24.00∫1.72 mmHg, respectively). The pressor effect of quinpirole was also significantly enhanced after combined pretreatment with intravenous and intrathecal domperidone, and its maximum (31.60∫2.31 mmHg) was significantly higher than that recorded in animals pretreated with intrathecal or intravenous domperidone alone. Intravenous pretreatment with metoclopramide (5 mg/kg) fully abolished the quinpirole-induced pressor effect. These results show that in conscious intact rats, blockade of spinal dopamine D 2 receptors enhances the pressor response to systemic quinpirole, suggesting that this agonist can decrease blood pressure through a spinal dopaminergic mechanism. Thus, our previous hypothesis that the entire effect of intravenous quinpirole on blood pressure in conscious rats can be composed of a central pressor action, a peripheral sympathoinhibitory depressor effect and also a spinal depressor effect is strongly supported by the present findings.