Exaggerated volume expansion natriuresis in rats preloaded with hypertonic saline: a paradoxical enhancement by inhibition of prostaglandin synthesis.

In preliminary experiments rats preinfused with hypertonic saline showed exaggerated natriuresis after an additional small volume expansion (SVE). This was systematically studied in anaesthetized Wistar rats prepared for clearance studies of the left kidney and measurements of medullary blood flow (MBF, laser-Doppler technique) and tissue electrical admittance (Y ), an index of interstitial ion concentration. The rats were preinfused i.v. with 3 mL of 5% NaCl during 90 min. A subsequent injection of isotonic saline, 0.5% of body weight, increased sodium excretion (UNaV ) from 2.1 +/- 0.5 to 4.5 +/- 1.1 micromol min-1 and urine flow (V ) from 12.0 +/- 2.3 to 24.3 +/- 5.6 microL min-1 (P < 0.02). The same volume of whole blood increased UNaV from 5.0 +/- 1.4 to 8.7 +/- 1.7 micromol min-1 and V from 22.3 +/- 5.1 to 37.4 +/- 5.9 microL min-1 (P < 0.01). The glomerular filtration rate, MBF and Y did not change. In rats preinfused with 0.9% saline no natriuresis was observed after SVE. To examine if prostaglandins (PG) were involved in SVE natriuresis, indomethacin (Indo), 5 mg kg-1 or sodium meclophenamate (Meclo), 7.5 mg kg-1, were added to the injected 0.9% saline. Paradoxically, both PG synthesis inhibitors enhanced natriuresis to SVE. After Indo UNaV increased from 2.0 +/- 0.6 to 7.6 +/- 1.3 micromol min-1, significantly more than after SVE alone (P < 0.001). At higher baseline UNaV, the increase with Meclo from 4.5 +/- 1.2 to 13.5 +/- 1.8 micromol min-1 was significantly higher than after whole blood infusion (P < 0.001). MBF decreased and Y increased after both inhibitors. Further studies are required to explain the enhancement of natriuresis after blockade of PG synthesis.