Comparative effects of antidiuretic hormone (ADH) administration and prostaglandin inhibition by indomethacin (IDM) on water excretion in Brattleboro rats

Comparative effects of antidiuretic hormone (ADH) administration and prostaglandin inhibition by indomethacin (IDM) on water excretion in Brattleboro rats

PROSTAGLANDINS COMPARATIVE EFFECTS OF ANTIDIURETIC HORMONE (ADH) ADMINISTRATION AND PROSTAGLANDIN INHIBITION BY INDOMETHACIN (IDM; ON WATER EXCRETION...

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PROSTAGLANDINS

COMPARATIVE EFFECTS OF ANTIDIURETIC HORMONE (ADH) ADMINISTRATION AND PROSTAGLANDIN INHIBITION BY INDOMETHACIN (IDM; ON WATER EXCRETION IN BRATTLEBORO RATS. BONHOMME,

M., FAVPE,

L., DURR,

J.

AND VPLLOTTON,

M.B.

Division of Endocrinology, Department of Medicine University Hospital, Ch-1211 Geneva 4, Switzerland.

Homozygous Brattleboro rats with complete diabetes insipidus are known to excrete much less renal prostaglandins than normal rats and to respond to large doses of Pitressin by a prompt increase in urinary prostaglandin release. To evaluate the influence of renal prostaglandins (PG) on the action of ADH, DI rats were treated with physiological dosis of ADH and IDM given separately or in combination. Female Brattleboro rats were studied under stable conditions. Urinary PGE2,PGF,, and ADH were determined in 24 h urines bv radioimmunoassay. Results I)

Chronic administration of ADH (Pitressin 40 mIU/Day) resulted in a marked stimulatior of PGE and F2cr excretion, which paralleled the hydroosmotic effect 3 of ADH.

2)

!DM (2 mg/kg/day) given alone had a weak antidiuretic action. The very low levels of urinary PG usual in 01 rats were not further reduced under IDM. Urinary ADH remained undetectable.

3)

When IDM was administered to rats chronically treated with ADE, no further antidiuretic effect was ncted. Urinary excreticn of PG enhanced by ADH was not modified. However when IDM was given concomitantly with ADH for 3 davs, the combined hydroosmotic action was additive, without evident inhibition of urinary PG excretion.

Ccnclusion The results indicate that IDM has a proper antidiuretic action in DI rats which can potentialize the effects of exogenous ADH. As this action is not reflected in a decreased urinary excretion rate of PG, it is not certain that it is mediated by PG inhibition and mav be due to one of several other effects which IDM exerts on the kidney.

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SUPPLEMENT TO VOL. 27