In Reply.—Dr Vierhapper correctly points out that, in addition to the inhibition of cyclo-oxygenase activity, indomethacin also inhibits other enzyme systems, such as phosphodiesterase. Thus, the antidiuretic effect of indomethacin may be related to these other effects, rather than just to prostaglandin synthesis inhibition. However, an antidiuretic effect in patients with congenital nephrogenic diabetes insipidus has been observed not only with indomethacin, 1-5 but also with two unrelated nonsteroidal anti-inflammatory drugs, acetylsalicylic acid5 and tolmetin.6 Similarly, in healthy waterloaded subjects, an antidiuretic effect has been reported not only with indomethacin, but also with carprofen7 and oxaprozin.8 Whereas Vierhapper et al9 found no significant effect of acetylsalicylic acid on diuresis in normal subjects, Berg10 demonstrated a substantial reduction in urine flow with this drug in patients with chronic renal insufficiency.
It is not possible to definitively conclude that the antidiuretic effect of indomethacin is