Open AccessBlockade of Spinal Dopamine D 2 Receptors Enhances the Pressor Effect of Intravenous Quinpirole in Normotensive, Conscious Rats
Author(s) -
Lahlou Saad
Publication year - 2002
Publication title -
pharmacology & toxicology
Language(s) - English
Resource type - Journals
eISSN - 1600-0773
pISSN - 0901-9928
DOI - 10.1034/j.1600-0773.2002.900207.x
Subject(s) - quinpirole , domperidone , agonist , dopamine receptor , medicine , dopamine , endocrinology , dopamine agonist , anesthesia , blood pressure , dopaminergic , receptor
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 μg/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.