The prostaglandin-analogue-9-deoxo-16,16-dimethyl-9-methylene-PGE2 inhibits the antidiuretic effect of vasopressin (AVP) in the conscious sheep

The effects of intravenous infusions of the stable prostaglandin analogue 9-deoxo-16,16-dimethyl-9-methylene-PGE2 (9-methylene-PGE2) in a dosage of 10 or 24 micrograms/min were studied in the consicious euhydrated, dehydrated, and hyperhydrated with the simultaneous administration of exogenous arginine vasopressin (AVP), sheep. The infusions decreased urine osmolality and increased urine flow and renal free water clearance. The results indicate that 9-methylene-PGE2 exhibits its diuretic effect by antagonizing the antidiuretic action of AVP. In the hyperhydrated sheep receiving AVP the syndrome of inappropriate antidiuretic hormone release (SIADH) was simulated. As the prostaglandin analogue effectively blocked the antidiuretic effect of the AVP-administration it appears that 9-methylene-PGE2 may play a future role as a diuretic agent, especially in conditions characterized by water retention and dilutional hyponatremia such as SIADH.