DOSE-DEPENDENT STIMULATION OF RENAL PROSTAGLANDIN SYNTHESIS BY DEAMINO-8-D-ARGININE VASOPRESSIN IN RATS WITH HEREDITARY DIABETES-INSIPIDUS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 217  (1) , 87-91
Abstract
It has been postulated that renal prostaglandins (PG) 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. The studies 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. PGF2.alpha. excretion was highly correlated with dose of dDAVP (r = 0.97, P < .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 < .001). dDAVP evidently stimulates renal PG synthesis in a dose-related fashion. This occurs at doses which bring urine osmolality into the normal physiological range. Stimulation of renal PG synthesis by arginine vasopressin is not due primarily to its pressor action. Urinary PGE2 and PGF2.alpha. excretion can vary independently.