Dose-dependent stimulation of renal prostaglandin synthesis by deamino- 8-D-arginine vasopressin in rats with hereditary diabetes insipidus

LA Walker and JC Frolich

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.

Volume 217, Issue 1, pp. 87-91, 04/01/1981
Copyright © 1981 by American Society for Pharmacology and Experimental Therapeutics