ABSTRACT

The cerebrospinal fluid level of arginine vasopressin (AVP) or vasoactive intestinal polypeptide (VIP) was enhanced chronically by implantation of a device for controlled drug delivery in the lateral ventricle of the rat. Urine production, water consumption, urine osmolality as well as urinary AVP excretion were then measured for a period of 26 days. During this period the rats were studied under normal hydration and under conditions of osmotic stress induced by water deprivation (2 days) and the drinking of 2% (w/v) NaCl (6 days), in order to see whether the capacity of central systems to react adequately to osmotic stimuli was affected by high central peptide levels.

Immediately after the central AVP treatment was started, a temporary increase was found in urinary AVP levels which was not accompanied by a change in any of the other parameters but which decreased again to control levels within 10 days. After this burst of AVP excretion, AVP-treated rats showed a tendency during periods of normal hydration for a lower urine osmolality, combined with a higher water intake and urine production without changes in urinary AVP excretion. Since there was no clear-cut correlation between urinary AVP excretion and body water turnover, this could still indicate a slowly acquired and slight inhibition of pituitary AVP release by long-term centrally administered AVP. However, the capacity of these rats to respond to osmotic stimuli was not different from the controls.

In the VIP-treated rats a slight but significant reduction in urine production was found in all three periods of normal hydration. During the osmotic stress induced by the drinking of 2% NaCl the VIP-treated rats showed a lower increase in urine production and fluid intake and a lower decrease in urine osmolality when compared with the response of the control rats. This has tentatively been interpreted as a potentiation by VIP of the activation of pituitary AVP release under these conditions.

J. Endocr. (1988) 117, 207–214

Neurohypophysial hormones are thought to be involved in alterations in fluid balance during pregnancy and delivery. In the course of normal pregnancy intravascular volume is increased whereas sodium restriction is thought to reduce plasma volume and cardiac output. In the present study, we measured the effect of long-term severe sodium restriction on vasopressin (AVP) and oxytocin (OT) levels during normal pregnancy and after delivery.

Fifty-nine healthy nulliparous women were randomized either for a low sodium diet (20 mmol sodium daily) or for a normal diet from week 12 of pregnancy onwards. Circulating plasma levels and urinary excretion of AVP and OT, their neurophysins (Np-AVP and Np-OT) and AVP bound to platelets were determined at regular intervals during pregnancy and after delivery. After completion of the study, women on a sodium-restricted diet were compared with control women on a normal diet using repeated measurement ANOVA with adjustment for potentially confounding variables.

After randomization, a reduction in urinary sodium excretion of, on average, 40–82% was found. In general, no effect of sodium restriction could be demonstrated on the various parameters (0·53<P<0·98) with the exception of a significantly lower 24-h urinary AVP excretion by non-smokers with sodium restriction compared with non-smokers having a normal diet (P=0·018) For all parameters, clear changes were found in the course of pregnancy and puerperium (P<0·0001 to P<0·005). Platelet-bound AVP decreased and Np-OT increased during pregnancy. After birth, free plasma AVP, plateletbound AVP, OT, osmolality, sodium and potassium increased, while Np-AVP and Np-OT decreased.

Although elevated Np-AVP and Np-OT levels during pregnancy seem to indicate increased release of neurohypophysial hormones, pregnancy up to 36 weeks of gestation is accompanied by low circulating AVP and OT levels.

Long-term severe sodium restriction diminishes urinary AVP excretion in (non-smoking) pregnant women, without changing circulating levels of AVP and OT, despite the known reduction in circulating volume. The reduced circulating (platelet-bound) AVP levels during pregnancy, whether or not in combination with severe sodium restriction, support the absence of significant non-osmotic stimulation of AVP during pregnancy.

Journal of Endocrinology (1997) 152, 345–354