Liberation of antidiuretic hormone: pharmacologic blockade of ascending pathways

Abstract

Water diuresis was established and maintained in dogs anesthetized with chloralose. Both ureters were cannulated and a continuous recording of urine flow obtained. ADH release was obtained from stimulation of the central end of a vagus nerve (the vagus-pituitary reflex), and ulnar nerve (nociceptive response) as well as from stimulation of reactive areas in the brain stem. Meperidine (10-15 mg/kg) and morphine (1-4 mg/kg) blocked the response to ulnar nerve stimulation and some brain-stem responses, but not the vagus-pituitary reflex. Similarly, the adrenergic blocking agents, Hydergine (0.3-0.6 mg/kg), phenoxy-benzamine (2.0 mg/kg) and phentolamine (0.25 mg/kg) markedly reduced the ulnar response and some brain-stem responses but not the vagus-pituitary reflex. However, larger doses of phenoxy-benzamine (5 mg/kg) and Hydergine (1 mg/kg) did inhibit the vagus-pituitary reflex. The anticholinergic agents, atropine (1-10 mg/kg) and ethybenztropine (0.5-2.0 mg/kg), were not effective blocking agents themselves but did render the inhibitory action of the adrenergic blocking agents more effective. These results suggest the existence of at least two different ascending pathways for ADH liberation. In addition, the evidence is compatible with the participation of adrenergic as well as cholinergic mechanisms in ADH liberation.