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Cardiovascular responses to intrathecal dopamine receptor agonists after spinal transection in conscious rats
1Laboratoire de Physiologie et Pharmacologie, URA CNRS 1287, Faculté de Pharmacie, Université Joseph Fourier, La Tronche, France.
Objective:
The cardiovascular responses to transient intrathecal administration of dopamine agonists were studied daily in chronically prepared rats that had been spinally transected or were sham operated. The goals were (1) to determine the group differences in evoked heart rate and arterial pressure responses and (2) to determine, within the transected group, whether or not the long term responses could be dissociated. The hypothesis tested is that cord transection releases a tonic inhibition of cardiovascular responsiveness independently of the mechanism of receptor hypersensitivity.
Methods:
Changes in mean aortic blood pressure and heart rate induced by intrathecal administration of the mixed D1/D2 dopamine receptor agonist apomorphine (150 nmol per rat) were measured in conscious rats during a 10 d experimental period following spinal transection.
Results:
Complete spinal transection did not affect aortic pressure but increased basal heart rate values by about 33% with respect to normal rats (p < 0.001). When apomorphine was injected caudally to the section (at T9-T10) but not rostrally (at T2-T4), it induced a 50% greater and an 800% more long lasting decrease in mean aortic pressure and a 230% greater and 70% more long lasting decrease in heart rate in spinal than in sham operated rats. These increases in cardiovascular responses were corroborated by a leftward shift of the apomorphine dose-response curves. They were also found after intrathecal administration of highly selective D1 and D2 receptor agonists fenoldopam (50 nmol per rat) and quinpirole (150 nmol per rat), and were specifically blocked by intrathecal haloperidol (27 nmol per rat), a non-selective dopamine antagonist.
Conclusions:
Complete spinal transection induces different increases in hypotensive and bradycardic responses to the stimulation of caudally located spinal dopamine receptors which could be due to the destruction of a tonically inhibiting spinal system rather than to hypersensitivity of the dopamine receptors.