Prostaglandins have been postulated to participate in the regulation of salt excretion during acute volume expansion. The present papillary and cortical micropuncture studies were designed to examine the effect of prostaglandin synthesis inhibitors on segmental chloride transport during hydropenia (with and without meclofenamate) and 10% volume expansion (with and without both meclofenamate and indomethacin). Both inhibitors significantly decreased the urinary excretion rate of prostaglandins E2 and F2α. Clearance studies on the intact right kidney demonstrated no effect of either agent on glomerular filtration rate, but a significant reduction in chloride excretion during hydropenia and volume expansion was observed. To assess the specific site(s) of enhanced chloride reabsorption, absolute and fractional chloride delivery was measured in the late proximal tubule, thin descending limb of Henle, and the early and late distal tubules. In addition, the fraction of filtered chloride remaining at the base and tip of the papillary collecting duct was compared to that fraction remaining at the superficial late distal tubule. During hydropenia, meclofenamate had no effect on fractional chloride delivery out of the superficial late distal tubule or the juxtamedullary thin descending limb of Henle, but significantly reduced the fraction of chloride delivered to the base of the papillary collecting duct. During volume expansion, neither meclofenamate nor indomethacin had an effect on absolute chloride delivery out of the proximal tubule or the thin descending limb of Henle. However, absolute chloride delivery to the early distal tubule was significantly reduced, and was associated with a decrease in fractional chloride reabsorption in this segment. Furthermore, the fraction of chloride delivered to the base of the collecting duct was significantly reduced. Fractional reabsorption along the terminal 1 mm of the collecting duct was not altered by either meclofenamate or indomethacin. These results suggest that inhibitors of prostaglandin synthesis result in an increase in chloride reabsorption in the superficial loop of Henle, and in segments between the superficial late distal tubule and the base of the collecting duct. The results are consistent with the view that prostaglandins inhibit chloride transport in the thick ascending limb of Henle, and/or the cortical and outer medullary collecting tubule.
Eiji Higashihara, John B. Stokes, Juha P. Kokko, William B. Campbell, Thomas D. Dubose Jr.