Release of vasopressin in response to hypoxia and the effect of aminergic and opioid antagonists

Plasma vasopressin, arterial blood gas tensions, pH, arterial blood pressure, heart rate and respiration were monitored in conscious rats breathing room air or exposed to varying degrees of hypoxia. A similar series of observations was made in a group of anaesthetized rats and in rats treated with α- and β-adrenergic and dopaminergic blocking agents. The effect of two opioid antagonists on the vasopressin response was also noted. Hypoxia produced an increase in circulating vasopressin concentrations in both conscious and anaesthetized rats. In the conscious animals the increase reached statistical significance when the animals were exposed to 12% oxygen in nitrogen, which produced a fall in arterial PaO2 of 44·7 ± 5·0%. Guanethidine, phentolamine and propranolol all produced a significant fall in the basal concentrations of vasopressin, while guanethidine, phenoxybenzamine and propranolol blocked the increase seen on breathing 12% oxygen in nitrogen. Naloxone and levallorphan also reduced the vasopressin response to hypoxia. Thus it appears that aminergic pathways play a role in the maintenance of circulating concentrations of vasopressin and in the response to hypoxia. Endogenous opioids also appear to be involved in the hypoxic response.

TIAPRIDE-INDUCED CHRONIC HYPERPROLACTINAEMIA: INTERFERENCE WITH THE HUMAN MENSTRUAL CYCLE

ABSTRACT Four regularly menstruating volunteers were submitted to an oral treatment, for 3 consecutive cycles and starting on the first day of a cycle, with tiapride at daily doses ranging from 1 × 100 mg to 2 × 100 mg. The first and the last cycle under treatment, as well as a prior control cycle, were thoroughly studied by means of daily measurements of blood concentrations of LH, FSH, prolactin (PRL), oestradiol and progesterone. Tiapride, a benzamide derivative with dopaminergic blocking activity at the level of the lactotrophes, increased mean PRL secretion in each subject but a permanent hyperprolactinaemia above 700 μU/ml was attained only in one subject. Despite these widely fluctuating PRL levels in most subjects, the resulting overall hyperprolactinaemia induced in all cases a progressive deterioration of the function of the corpus luteum: 5 cycles showed luteal phases reduced by 2–5 days, one cycle was characterized by some slight luteinisation but questionable ovulation and the 2 remaining cycles were anovulatory. The interruption of drug intake one week after the onset of menses led thereafter to a cycle with a likely inadequate luteal phase but of normal length. It is concluded that even a non-permanent hyperprolactinaemia can impair the normal function of the hypothalamo-pituitaryovarian axis, as well as exhibit some effects in a cycle consecutive to the normalization of PRL. With the exception of the impaired luteal progesterone secretion, the pooled hormonal data from the short luteal phase cycles under tiaprideinduced hyperprolactinaemia exhibit very little significant differences, as compared to the corresponding values in the control cycles. Some delay in the onset of follicular maturation, however, should be assumed since the follicular phase had been lengthened by 1 to 31 days in 5 of the 6 cycles with luteinisation during treatment. The present results are compatible with a double impact – both at the ovarian and the hypothalamo-pituitary levels – of hyperprolactinaemia in its mechanisms of impaired function of the hypothalamo-pituitary ovarian axis.