Antidiuretic and PGE2 responses to AVP and dDAVP in subjects with central and nephrogenic diabetes insipidus

Vasopressin stimulates renal prostaglandin (PGE2) production at several loci and in turn PGE2 modulates the antidiuresis. We have found the time courses of increased urinary PGE2 in subjects with central diabetes insipidus (DI) parallel the antidiuretic responses to AVP and dDAVP. The antidiuretic response to 4 micrograms dDAVP in these subjects was far greater than the response to 5 U (12.5 micrograms) AVP, but the PGE2 response to the dDAVP was only marginally greater than that which followed the AVP. Therefore, dDAVP disproportionately stimulates antidiuresis in relation to PGE2 production, whereas the reverse holds for AVP. In subjects with nephrogenic DI 12.5 micrograms AVP caused no antidiuresis but stimulated PGE2 excretion as well as in subjects with central DI. There was an intermediate relationship between antidiuresis and PGE2 excretion in subjects with central DI given AVP and subjects with nephrogenic DI injected with dDAVP. In summary, 1) the normal PGE2 response to AVP in subjects with nephrogenic DI is consistent with other evidence that non-antidiuretic actions of vasopressin are not impaired in these subjects. 2) The limited capability of dDAVP to stimulate PGE2 may be a factor in the augmented antidiuretic response to dDAVP in subjects with central DI. 3) Antidiuretic and PGE2 responses to vasopressin can be dissociated, thus allowing further consideration of mechanisms by which each may be independently controlled and interrelated.