Lahlou S, Petitjean P, Pellissier G, Mouchet P, Feuerstein C, Demenge P
Laboratoire de Physiologie Pharmacologie II, URA CNRS, Faculté de Pharmacie, Université Joseph Fourier, Grenoble, France.
J Cardiovasc Pharmacol. 1990 Aug;16(2):331-7. doi: 10.1097/00005344-199008000-00021.
In conscious freely moving rats, administration of apomorphine (179 nmol), a dopamine receptor agonist, into the intrathecal (i.t.) space decreased mean aortic blood pressure (MBP) and heart rate (HR). Both the magnitude and the time of appearance of the response varied according to the spinal level of administration. The largest and immediately appearing effect was observed after the injection at the upper thoracic site, whereas the magnitude of the responses was smaller with an immediate or slightly delayed (0.5-1.5 min) onset at lower thoracic and midcervical levels. More caudal responses appeared to be due to spreading of the drug along the spinal axis (onset in 1-2 min after administration). Behavioral responses (stereotyped movements) were observed within 2-3 min after administration and were nearly the same whatever the site of administration. These results corroborate, as do those provided by i.t. injections of tritiated apomorphine, the spinal origin of cardiovascular effects of i.t. apomorphine. Furthermore, spinal transection at the T5-T7 level did not change the magnitude and duration of decreases in MBP and HR elicited by i.t. apomorphine injected at the T2-T4 level. Moreover, this procedure enhanced responses to i.t. administration at the T9-T10 level. In conclusion, these results favor the existence of a spinal site of action for the cardiovascular effects of apomorphine. Furthermore, they indicate that spinal transection is accompanied by development of a hypersensitive phenomenon (of a mechanism to be determined).
在清醒自由活动的大鼠中,向鞘内(i.t.)注射多巴胺受体激动剂阿扑吗啡(179 nmol)可降低平均主动脉血压(MBP)和心率(HR)。反应的幅度和出现时间因给药的脊髓水平而异。在上胸部部位注射后观察到最大且立即出现的效应,而在下胸部和颈中部水平,反应幅度较小,起效立即或稍有延迟(0.5 - 1.5分钟)。更靠尾端的反应似乎是由于药物沿脊髓轴扩散所致(给药后1 - 2分钟起效)。给药后2 - 3分钟内观察到行为反应(刻板运动),且无论给药部位如何,反应几乎相同。这些结果与鞘内注射氚标记阿扑吗啡所提供的结果一样,证实了鞘内注射阿扑吗啡对心血管作用的脊髓起源。此外,在T5 - T7水平进行脊髓横断并不改变在T2 - T4水平鞘内注射阿扑吗啡所引起的MBP和HR降低的幅度和持续时间。而且,该操作增强了在T9 - T10水平对鞘内给药的反应。总之,这些结果支持阿扑吗啡对心血管作用存在脊髓作用部位。此外,它们表明脊髓横断伴随着一种超敏现象(一种有待确定的机制)的发展。