Minson J B, Choy V J, Chalmers J P
J Cardiovasc Pharmacol. 1984 Mar-Apr;6(2):312-7. doi: 10.1097/00005344-198403000-00016.
Systemic methyldopa administration in genetically hypertensive rats evoked a hypotension which was attenuated after prior treatment with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) given either intracerebroventricularly, to produce a generalised ablation of serotonin nerves in brain and spinal cord, or by injection into the cervical spinal cord, to cause a selective destruction of descending serotonin pathways. Direct microinjection of methyldopa into the ventrolateral medulla in the area of the B1 and B3 serotonin cells was also effective in lowering arterial pressure. The hypotensive response to this medullary administration of methyldopa was again attenuated by 5,7-DHT given either intracerebroventricularly or by intraspinal injection. On the other hand, prior treatment intracerebroventricularly with 6-hydroxydopamine did not affect the hypotensive effect of methyldopa injected into the region of the ventrolateral B1 and B3 cells, supporting the suggestion that this effect of methyldopa is mediated by bulbospinal serotonin neurons and not by descending catecholamine nerves. The fact that methyldopa injection into the ventrolateral medulla in a region coinciding with the B1 and B3 cells lowers blood pressure is consistent with previous studies demonstrating that these neurons serve to maintain or elevate arterial pressure.
给遗传性高血压大鼠全身注射甲基多巴可引起血压降低,而在预先用神经毒素5,7 - 二羟基色胺(5,7 - DHT)处理后,这种低血压作用会减弱。5,7 - DHT可以通过脑室内注射以导致脑和脊髓中5 - 羟色胺能神经的广泛消融,或者通过注入颈脊髓以选择性破坏下行5 - 羟色胺能通路。将甲基多巴直接微量注射到B1和B3 5 - 羟色胺能细胞所在区域的延髓腹外侧,也能有效降低动脉血压。对延髓注射甲基多巴所产生的降压反应,在脑室内注射或脊髓内注射5,7 - DHT后再次减弱。另一方面,预先脑室内注射6 - 羟基多巴胺并不影响注射到延髓腹外侧B1和B3细胞区域的甲基多巴的降压作用,这支持了甲基多巴的这种作用是由延髓脊髓5 - 羟色胺能神经元介导而非由下行儿茶酚胺能神经介导的观点。向与B1和B3细胞相对应区域的延髓腹外侧注射甲基多巴可降低血压,这一事实与先前的研究一致,这些研究表明这些神经元有助于维持或升高动脉血压。