Involvement of spinal dopamine receptors in mediation of the hypotensive and bradycardic effects of systemic quinpirole in anaesthetised rats

Abstract

This study examined the involvement of spinal dopamine D 2 receptors in the cardiovascular effects induced by intravenous administration of the selective dopamine D 2 receptor agonist quinpirole, as has been previously reported for the hypotensive action of systemic bromocriptine. In normotensive pentobartitone-anaesthetised rats, intravenous injection of quinpirole (25 to 1000 μg/kg) decreased mean aortic pressure and heart rate in a dose-related manner. The intravenous (0.5 mg/kg) or intrathecal (40 μg/rat at T9–T10) pretreatment with domperidone, a dopamine D 2 receptor antagonist that does not cross the blood-brain barrier, significantly reduced the maximal hypotensive and bradycardic responses to intravenous quinpirole (1000 μg/kg). In contrast, the latter effects were fully abolished either by intravenous metoclopramide (5 mg/kg) or combined pretreatment with intravenous and intrathecal domperidone. In addition, when injected intrathecally at the T9–T10 level of the spinal cord, quinpirole (7.7 to 61.4 μg/rat) also produced dose-dependent depressor and bradycardic effects which could be blocked by intrathecal, but not intravenous, domperidone pretreatment. This suggests that, in anaesthetised normotensive rats, the hypotensive and bradycardic responses to intravenous quinpirole are fully mediated by dopamine D 2 receptors, some of which are located in the peripheral circulation and some of which are located within the spinal cord. The latter finding is novel, suggesting that partial spinal mediation may not be peculiar to bromocriptine, as was previously thought. Rather, partial spinal mediation may be common to most dopamine D 2 receptor agonists.