Increased urinary excretion of PGE2 during inappropriate antidiuresis induced by DDAVP

Abstract

Increased urinary prostaglandin E excretion (UPGE2V) and renal production of PGE2 have been implicated in the mediation of escape from inappropriate antidiuresis induced by vasopressin (AVP). AVP-induced increases in PGE2 have been linked to its pressor activity. We examined the effects of the non-pressor AVP analogue, 1,desamino-8-D-arginine vasopressin (DDAVP), on UPGE2V in a rat model of inappropriate antidiuresis in which the escape response is not apparent. A dose of DDAVP known to cause antidiuresis (10 ng/hr), was given by osmotic minipump to rats during a water diuresis established by ad libitum ingestion of 5% dextrose in water (D/W). This dose of DDAVP reduced plasma sodium (P[Na+] ) to 127 +/- 2 mEq/liter within 24 hr. P[Na+] in controls given 5% D/W alone was 151 +/- 2. In the first eight hr after DDAVP, UPGE2V was fivefold higher than in control animals, an increase which was sustained for 48 hrs. Plasma renin (PRA) was threefold higher in control rats compared to rats that had received DDAVP, consistent with volume expansion in the latter. Despite declines in P[Na+] and PRA and increased UPGE2V in DDAVP treated rats, evidence of escape from inappropriate antidiuresis (secondary decline in Uosm or rise in urine volume (V) or P[Na+] ) was lacking. Moreover, DDAVP induced similar fivefold increases in UPGE2V when given to fluid deprived rats, demonstrating that increases of UPGE2V during inappropriate antidiuresis were not mediated by volume expansion. Administration of indomethacin to volume repleted DDAVP treated rats did not significantly increase Uosmol or decrease V compared to values observed in rats receiving DDAVP alone.(ABSTRACT TRUNCATED AT 250 WORDS)