It has been postulated that renal
prostaglandins (PGs) function as negative feedback inhibitors of the action of
antidiuretic hormone (ADH), implying a correlation between levels of ADH and the rate of renal PG synthesis. These studies have evaluated the relationship between renal PG synthesis and
hormone levels in rats with hereditary
diabetes insipidus, a species devoid of circulating ADH. Since
vasoconstrictor agents can stimulate renal PG synthesis by mechanisms unrelated to antidiuretic activity, deamino-8-D-arginine
vasopressin (
dDAVP) was utilized for replacement
therapy instead of
arginine vasopressin, which has considerable pressor activity.
dDAVP was administered by S.C. implanted osmotic minipumps to obtain steady states of
dDAVP at different dose levels. As indices of renal PG synthesis, urinary excretion of
PGE2 and
PGF2 alpha were measured by gas chromatography-mass spectrometry.
PGE2 excretion, although increased by
dDAVP treatment, was not correlated with dose of
dDAVP. However,
PGF2 alpha excretion was highly correlated with dose of
dDAVP (r = 0.97, P less than .01). The sum (
PGE2 +
PGF2 alpha), which may more accurately reflect total medullary PG synthesis, was also significantly correlated with dose of
dDAVP (r = 0.98, P less than .001). It is concluded that
dDAVP stimulates renal PG synthesis in a dose-related fashion. This occurs at doses which bring urine osmolality into the normal physiological range. Furthermore, it is shown that stimulation of renal PG synthesis by
arginine vasopressin is not due primarily to its pressor action. These experiments also provide evidence that urinary
PGE2 and
PGF2 alpha excretion can vary independently.