Effect of meclofenamate on lithium excretion in response to changes in renal perfusion pressure

Previous studies in dogs have demonstrated that inhibition of prostaglandin synthesis markedly impairs the ability of the kidney to alter sodium excretion in response to changes in renal perfusion pressure (RPP). The objectives of the present study were to determine whether renal prostaglandins play a role in the urinary sodium excretory response to alterations in RPP in the rat and to determine the role of the proximal tubule in this response. RPP was changed from 127 to 109 mm Hg and then to 91 mm Hg with a servo-controlled cuff on the abdominal aorta. Fractional lithium excretion (FELi) was used as an index of ractional sodium reabsorption by the proximal tubule. As a function of increases in RPP, FELi increased, suggesting that fractional sodium reabsorption by the proximal tubule was decreased in response to increases in RPP in control animals. In meclofenamate-treated rats, increases in fractional sodium excretion and FELi in response to increases in RPP were attenuated compared with levels in control animals. The blunted response of FELi in meclofenamate-treated rats suggests that the attenuated increase in urinary sodium excretion observed during increases in RPP reflects an increase in proximal sodium reabsorption mediated by blockade of renal prostaglandins.