Blockade of spinal dopamine D2 receptors enhances the pressor effect of intravenous quinpirole in normotensive, conscious rats.
The present investigation was undertaken to examine whether in conscious intact rats blockade of spinal dopamine D2 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 microg/rat at T9-T10) domperidone, a dopamine D2 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 D2 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.
Lahlou
Saad
S
Department of Physiology and Pharmacology, Center of Biological Sciences, Federal University of Pernambuco, Recife, Brazil. lahlou@npd.ufpe.br
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004294:Domperidone / Q000008:administration & dosage / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008297:Male; D019257:Quinpirole / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D018491:Dopamine Agonists; D065127:Dopamine D2 Receptor Antagonists; D019257:Quinpirole; D004294:Domperidone