Cerebrospinal fluid neurohypophysial peptides in benign intracranial hypertension.

The cerebrospinal fluid (CSF) concentrations of arginine vasopressin (AVP) and oxytocin (OT) were investigated both in patients with benign intracranial hypertension and in age and sex matched controls. Twenty eight lumbar punctures were performed on 15 patients with benign intracranial hypertension as part of their routine investigation and therapy. All patients had raised intracranial pressure (27.4, SE 1.7 cm.CSF). CSF AVP levels were significantly elevated in benign intracranial hypertension (2.1, SE 0.3 pmol/l) compared with controls (0.7, SE 0.1 pmol/l, p less than 0.001) but CSF OT concentrations were similar in both groups. CSF osmolality and plasma AVP and osmolality were identical in patients and controls. There was no correlation between CSF AVP concentration and intracranial pressure. The selective elevation of AVP in CSF may be of importance in the pathogenesis of raised intracranial pressure in benign intracranial hypertension.

The neurohypophysis: recent developments.

The hormones of the neurohypophysis, vasopressin and oxytocin, have now been shown to be synthesized as part of a prohormone complex that includes a vasopressin-neurophysin and oxytocin-neurophysin, respectively. In addition, for vasopressin, there is a glycopeptide as part of the prohormone. For each hormone the prohormone is packaged into neurosecretory granules and transported via axons to the posterior pituitary gland. In addition to this "classic" system, axons containing neurohypophyseal hormones project to the median eminence for release into portal vessels, and to other areas of the brain and spinal cord where the peptides may function as neurotransmitters rather than as hormones. As neurotransmitters, the neurohypophyseal hormones may be involved in the regulation of certain autonomic functions. Vasopressin and oxytocin are secreted into the cerebrospinal fluid where there is a diurnal rhythmic secretion of the peptides in several animal species (some species have a predominant rhythm of vasopressin and others a rhythm of oxytocin). Neurohypophyseal peptides are synthesized in some non-neuronal tissues where the function is unknown, and recently a novel peptide with similarities to oxytocin and vasotocin has been identified. The relationship of this novel peptide to the neurohypophyseal peptides is unknown. These new developments are likely to elucidate many new functions for the hormones of the neurohypophysis.

Penetration of neurohypophyseal hormones from plasma into cerebrospinal fluid (CSF): half-times of disappearance of these neuropeptides from CSF.

The penetration of neurohypophyseal peptides after peripheral administration into the cerebrospinal fluid (CSF) was studied in freely moving rats. In addition, the clearance of these peptides from CSF was investigated. Increased concentrations of vasopressin (AVP) in CSF were detectable 2 min after s.c. injection of 5.0 micrograms of this peptide. Peak concentration was reached at 5 min after administration and this level declined slowly over the next hour. Administration of 5.0 micrograms oxytocin (OXT) s.c. or i.v. resulted in increased OXT levels in CSF within 10 min after application. After 60 min a significant elevation of OXT in CSF was no longer present. These data reveal that approximately 0.002% of the peripherally applied amount of AVP or OXT reached the central nervous system at 10 min after injection. AVP (2.5 ng) and OXT (5.0 ng) applied into one of the lateral brain ventricles reached the cisternal cavity within 2 min after administration. Both neuropeptides were cleared from the CSF with terminal half-times of 26 and 19 min for AVP and OXT, respectively. The present data demonstrate that neurohypophyseal hormones do cross the blood-brain barrier in amounts obviously sufficient to induce central actions.