Nonsteroidal anti-inflammatory drugs cause sodium and water retention in the rat

Publisher Website
Google Scholar
Abstract
Nonsteroidal anti-inflammatory drugs (NSAID) were examined to determine whether they caused salt and water retention in the rat. Despite widely differing structures, at high concentrations most of these compounds displaced [3H]aldosterone from rat renal receptors. Displacement potency was in the sequence: indomethacin > mefenamic acid = meclofenamic acid > phenylbutazone > ibuprofen > aspirin; naproxen failed to bind. All NSAID tested caused a significant reduction in urine flow and Na+/creatinine excretion in adrenalectomized rats. The salt retention may not be mediated via mineralocorticoid receptors but may be the result of prostaglandin synthesis inhibition. Naproxen caused salt retention but failed to bind. The dose of NSAID causing salt retention correlated with the anti-inflammatory dose which was presumably the prostaglandin inhibitory dose. Indomethacin significantly inhibited the excretion of prostaglandin E2 under the experimental conditions. This dose failed to achieve displacement of [3H]aldosterone from receptors in vivo. Spironolactone administration, which blocked the aldosterone-induced salt retention, failed to inhibit the NSAID-induced salt retention. Prostaglandin antagonists of other types also caused Na retention.