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 H2O) in control and 6-OHDA rats. The control rats, however, increased urinary osmolality (Uosm) to 586 mosmol/kg H2O, whereas 6-OHDA rats increased Uosm only to 335 mosmol/kg H2O (P < 0.005). These changes in Uosm were accompanied by an increase in plasma ADH to 7.6 μIU/ml in control animals vs. 2.9 μIU/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 H2O in control rats, whereas Uosm in 6-OHDA rats increased to only 358 mosmol/kg H2O (P < 0.001). At the same time, ADH levels also were significantly greater in Cont rats (2.4 μIU/ml) than in the 6-OHDA animals (0.69 μIU/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.


Thomas R. Miller, William A. Handelman, Patricia E. Arnold, Keith M. McDonald, Perry B. Molinoff, Robert W. Schrier


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