Blunted presser responsiveness to intravenous quinpirole in conscious, chronic spinal cord-transected rats: peripheral vs. spinal mechanisms

Intravenous quinpirole (1 mg/kg) in conscious rats with chronic spinal cord transection (at T5-T7) induced an initial presser effect, which was signif icantly reduced in both magnitude and duration compared with that in sham-o perated rats, which was then followed by a long-lasting depressor effect. T o distinguish the spinal and/or peripheral origin of this phenomenon, consc ious, spinal cord-transected rats were also pretreated with either intraven ous (0.5 mg/kg), intrathecal (40 mug/kg) or combined intravenous and intrat hecal domperidone, a dopamine D-2 receptor antagonist that does not cross t he blood-brain barrier. Intravenous pretreatment with domperidone enhanced, but did not completely restore, the presser effect of quinpirole, and had no effect upon the depressor component. However, both the depressor compone nt and the reduction of the presser effect induced by spinal section were f ully abolished by intrathecal or combined intrathecal and intravenous dompe ridone. Quinpirole-induced changes in mean aortic pressure were also fully abolished by intravenous pretreatment with metoclopramide (5 mg/kg). Neithe r the presser nor the bradycardiac response to intravenous phenyl ephrine d iffered between sham-operated and spinal rats. These results suggest that t he blunted presser response to quinpirole after spinal cord transection is related to an enhanced spinal dopamine D-2 receptor-mediated depressor effe ct rather than to hypersensitivity of peripheral dopamine D-2 receptors or vascular hyporesponsiveness to alpha (1)-adrenoceptor stimulation. Thus, in conscious intact rats, the prominent central presser effect of quinpirole seems to oppose, not only a peripheral sympathoinhibitory depressor effect, as previously thought, bur also a spinal depressor effect. (C) 2000 Elsevi er Science B.V. All rights reserved.