Blunted pressor 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 pressor effect, which was significantly reduced in both magnitude and duration compared with that in sham-operated rats, which was then followed by a long-lasting depressor effect. To distinguish the spinal and/or peripheral origin of this phenomenon, conscious, spinal cord-transected rats were also pretreated with either intravenous (0. 5 mg/kg), intrathecal (40 microg/kg) or combined intravenous and intrathecal domperidone, a dopamine D(2) receptor antagonist that does not cross the blood-brain barrier. Intravenous pretreatment with domperidone enhanced, but did not completely restore, the pressor effect of quinpirole, and had no effect upon the depressor component. However, both the depressor component and the reduction of the pressor effect induced by spinal section were fully abolished by intrathecal or combined intrathecal and intravenous domperidone. Quinpirole-induced changes in mean aortic pressure were also fully abolished by intravenous pretreatment with metoclopramide (5 mg/kg). Neither the pressor nor the bradycardiac response to intravenous phenylephrine differed between sham-operated and spinal rats. These results suggest that the blunted pressor response to quinpirole after spinal cord transection is related to an enhanced spinal dopamine D(2) receptor-mediated depressor effect 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 pressor effect of quinpirole seems to oppose, not only a peripheral sympathoinhibitory depressor effect, as previously thought, but also a spinal depressor effect.
Lahlou
S
S
Departamento de Fisiologia e Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Cidade Universitária, 50670-901, Recife, PE, Brazil. lahlou@npd.ufpe.br
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002818:Cordotomy; D004294:Domperidone / Q000494:pharmacology; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D019257:Quinpirole / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000819:agonists; D013116:Spinal Cord / Q000502:physiology*
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D010656:Phenylephrine; D019257:Quinpirole; D004294:Domperidone