Prostaglandins in the fetal circulation following maternal ingestion of a prostaglandin synthetase inhibitor during mid-pregnancy.

To assess the possible effect upon the fetus of maternal ingestion of the prostaglandin synthetase inhibitor, mefenamic acid, taken during mid-pregnancy (15-22 weeks) to prevent spontaneous abortion, samples of fetal blood were collected at fetoscopy from 13 treated and 14 untreated control cases. Mefenamic acid levels in the fetus were 32-54% of those in the mothers in the treated group, while prostaglandins E2 (PGE2), 6-oxo-PGF1 alpha and PGFM were all slightly but not significantly lower in those patients given 500 mg mefenamic acid 40-180 min prior to sampling than in untreated controls. Results indicate that the prostaglandin synthetase inhibitor crosses the placenta at this early gestation and may possibly suppress fetal prostaglandin production.

PGE2 and 6-keto-PGF1 alpha excretion in Brattleboro rats with hereditary hypothalamic diabetes insipidus.

Brattleboro rats, a strain with hereditary hypothalamic diabetes insipidus, were found to excrete significantly higher amounts of both renal (PGE2) and vascular (6-keto-PGF1 alpha) prostaglandins than control Long-Evans rats. The increased prostaglandin synthesis was reversed by vasopressin treatment. These results suggest that in the intact organism prostaglandin synthesis in the kidneys and in the endothelial cells of blood vessels may be under tonic inhibitory control by vasopressin. The findings further support the view that prostaglandins play an important role in the regulation of water excretion and in the pathogenesis of polyuric conditions.

Renal thromboxane excretion in Brattleboro rats with hereditary hypothalamic diabetes insipidus. Effect of vasopressin treatment.

Rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain) which are devoid of vasopressin, excrete significantly increased amounts of immunoreactive thromboxane B2 in urine. The increase was corrected by treatment with vasopressin. These results suggest that, in the intact organism, thromboxane synthesis may be under tonic inhibitory control by vasopressin although other renal mechanisms explaining the increase in thromboxane cannot be excluded. Our observations further support an involvement of prostaglandins and thromboxanes in the regulation of water metabolism.

Hypokalaemia stimulates prostacyclin synthesis in the rat.

1. To examine the hypothesis that the normalcy of blood pressure, despite an increase in circulating angiotensin II, and the blood pressor hyporesponsiveness to infusion of pressor agents which are associated with hypokalaemia, are due to overproduction of prostacyclin, the principal prostaglandin (PG) synthesized by the vascular endothelium, we studied the effect of experimental hypokalaemia on the urinary excretion of immunoreactive 6-keto-prostaglandin F1 alpha, a stable metabolite of prostacyclin, in the rat. 2. The animals were fed on a potassium-deficient diet for 9 days. Twenty-four hour urine samples were collected daily for measurement of urinary excretion of immunoreactive 6-keto-PGF1 alpha, PGE2 and 13,14-dihydro-15-keto-PGF2 alpha (PGFM). 3. Hypokalaemia caused significant increases of the three prostaglandins measured. 4. We conclude that hypokalaemia is a potent stimulus of both renal and vascular prostaglandins. The results suggest that an increase in prostacyclin synthesis in peripheral blood vessel walls may be responsible for the resistance of blood pressure to infusion of pressor substances as well as for the normalcy of blood pressure, despite the presence of high circulating angiotensin II concentrations, in conditions associated with hypokalaemia.

Excretion of 6-keto-PGF1 alpha and PGE2 in rats with hereditary hypothalamic diabetes insipidus.

We measured the urinary excretion of a stable metabolite of prostacyclin, 6-keto-PGF1 alpha, and of PGE2 in homozygous Brattleboro rats, a strain with hereditary hypothalamic diabetes insipidus. Excretion of both prostaglandins was largely increased compared to both heterozygous Brattleboro rats and Long-Evans rats. These results are in contrast to previously published observations demonstrating a subnormal excretion of PGE2 in Brattleboro rats. It is suggested that prostaglandin synthesis may be under tonic inhibitory control by vasopressin both in the kidney and in the endothelial cells of blood vessels. The findings further support the view that prostaglandins play an important role in the regulation of water excretion and in the pathogenesis of polyuric conditions.