Miller T R, Handelman W A, Arnold P E, McDonald K M, Molinoff P B, Schrier R W
J Clin Invest. 1979 Dec;64(6):1599-607. doi: 10.1172/JCI109621.
The central nervous system (CNS) mechanism(s) for the release of antidiuretic hormone (ADH) by various stimuli is unknown. In this study, the role of CNS catecholamines in effecting ADH release was examined in conscious rats 10-14 d after the cerebroventricular injection of 6-hydroxydopamine (6-OHDA). This dose of 6-OHDA caused a 67% depletion of brain tissue norepinephrine and only 3% depletion of heart norepinephrine, as compared with controls, which were injected with the vehicle buffer alone. Either intravenous 3% saline (osmotic stimulus) or intraperitoneal hyperoncotic dextran (nonosmotic stimulus) was administered to water-diuresing rats through indwelling catheters. Neither of these maneuvers changed arterial pressure, pulse, or inulin clearance in control or 6-OHDA rats. The 3% saline caused similar increases in plasma osmolality (15 mosmol/kg H(2)O) in control and 6-OHDA rats. The control rats, however, increased urinary osmolality (Uosm) to 586 mosmol/kg H(2)O, whereas 6-OHDA rats increased Uosm only to 335 mosmol/kg H(2)O (P < 0.005). These changes in Uosm were accompanied by an increase in plasma ADH to 7.6 muIU/ml in control animals vs. 2.9 muIU/ml in 6-OHDA rats (P < 0.005). All waterdiuresing animals had undetectable plasma ADH levels. Dextran-induced hypovolemia caused similar decrements (- 10%) in blood volume in both control and 6-OHDA animals, neither of which had significant changes in plasma osmolality. This nonosmotic hypovolemic stimulus caused an increase in Uosm to 753 mosmol/kg H(2)O in control rats, whereas Uosm in 6-OHDA rats increased to only 358 mosmol/kg H(2)O (P < 0.001). At the same time, ADH levels also were significantly greater in Cont rats (2.4 muIU/ml) than in the 6-OHDA animals (0.69 muIU/ml; P < 0.05). These results therefore suggest that CNS catecholamines may play an important role in mediating ADH release in response to both osmotic and nonosmotic (hypovolemic) stimuli.
各种刺激释放抗利尿激素（ADH）的中枢神经系统（CNS）机制尚不清楚。在本研究中，在脑室注射6-羟基多巴胺（6-OHDA）后10 - 14天的清醒大鼠中，研究了中枢神经系统儿茶酚胺在影响ADH释放中的作用。与仅注射载体缓冲液的对照组相比，该剂量的6-OHDA导致脑组织去甲肾上腺素耗竭67%，而心脏去甲肾上腺素仅耗竭3%。通过留置导管向水利尿大鼠静脉注射3%盐水（渗透刺激）或腹腔注射高渗右旋糖酐（非渗透刺激）。这些操作均未改变对照组或6-OHDA大鼠的动脉血压、脉搏或菊粉清除率。3%盐水使对照组和6-OHDA大鼠的血浆渗透压升高相似（15 mosmol/kg H₂O）。然而，对照组大鼠尿渗透压（Uosm）升高至586 mosmol/kg H₂O，而6-OHDA大鼠Uosm仅升高至335 mosmol/kg H₂O（P < 0.005）。Uosm的这些变化伴随着对照组动物血浆ADH升高至7.6 μIU/ml，而6-OHDA大鼠为2.9 μIU/ml（P < 0.005）。所有水利尿动物的血浆ADH水平均检测不到。右旋糖酐诱导的血容量减少在对照组和6-OHDA动物中导致相似的血容量减少（-10%），两者的血浆渗透压均无显著变化。这种非渗透性血容量减少刺激使对照组大鼠Uosm升高至753 mosmol/kg H₂O，而6-OHDA大鼠Uosm仅升高至358 mosmol/kg H₂O（P < 0.001）。同时，对照组大鼠（2.4 μIU/ml）的ADH水平也显著高于6-OHDA动物（0.69 μIU/ml；P < 0.05）。因此，这些结果表明中枢神经系统儿茶酚胺可能在介导ADH释放以响应渗透和非渗透（血容量减少）刺激方面发挥重要作用。
