Kuwaki T, Koshiya N, Takahashi H, Terui N, Kumada M
Department of Physiology, Faculty of Medicine, University of Tokyo, Japan.
Jpn J Physiol. 1990;40(1):97-116. doi: 10.2170/jjphysiol.40.97.
To characterize the modulatory action of rat endothelin (endothelin-3 or ET-3) on the cardiovascular control by the central nervous system (CNS), ET-3 was injected into the cisterna magna of urethane-anesthetized and immobilized rats. An injection of 100 pmol of ET-3 caused immediate rises in arterial pressure (AP), renal nerve activity (RNA), and heart rate (HR). These variables subsequently decreased and, in 5-20 min, fell below the pre-injection level. Simultaneously, the arterial baroreceptor reflex was almost totally suppressed. Although RNA and HR subsequently returned to, or often exceeded, pre-injection levels in 20 to 60 min and reflex activity recovered, AP sometimes remained below control for at least 2 h. A similar pattern of changes was elicited in unanesthetized precollicular decerebrated rats. The responses to ET-3 were abolished by hexamethonium chloride, but were not conspicuously altered by arginine vasopressin antagonist or angiotensin II antagonist. The CNS sites responsible for ET-induced changes were subsequently searched. Topical application of ET-3 to the ventral surface of the medulla (VSM) caused the pattern of changes in AP, RNA, and HR similar to that following intracisternal injection. Microinjection of ET-3 into the nucl. tractus solitarius (NTS) increased AP and RNA, whereas intrathecal administration of it decreased them. We conclude that intracisternally administered ET-3 centrally modulates both tonic and reflex control of AP by the sympathetic nervous system and that the VSM appears to be primarily responsible for the modulation, although NTS and spinal cord may also be involved in it.
为了阐明大鼠内皮素（内皮素 -3 或 ET-3）对中枢神经系统（CNS）心血管控制的调节作用，将 ET-3 注入氨基甲酸乙酯麻醉并固定的大鼠的小脑延髓池。注射 100 pmol 的 ET-3 可使动脉压（AP）、肾神经活动（RNA）和心率（HR）立即升高。这些变量随后下降，并在 5 - 20 分钟内降至注射前水平以下。同时，动脉压力感受器反射几乎完全被抑制。尽管 RNA 和 HR 在 20 至 60 分钟后随后恢复到或常常超过注射前水平且反射活动恢复，但 AP 有时至少 2 小时仍低于对照水平。在未麻醉的脑桥前切除大脑的大鼠中也引发了类似的变化模式。ET-3 的反应被氯化六甲铵消除，但精氨酸加压素拮抗剂或血管紧张素 II 拮抗剂并未使其发生明显改变。随后寻找了负责 ET 诱导变化的中枢神经系统部位。将 ET-3 局部应用于延髓腹侧表面（VSM）引起的 AP、RNA 和 HR 的变化模式与脑池内注射后相似。向孤束核（NTS）微量注射 ET-3 可使 AP 和 RNA 升高，而鞘内给药则使其降低。我们得出结论，脑池内注射的 ET-3 在中枢调节交感神经系统对 AP 的紧张性和反射性控制，并且 VSM 似乎是这种调节的主要负责部位，尽管 NTS 和脊髓也可能参与其中。
