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

In preliminary experiments rats preinfused with hypertonic saline showed ex aggerated natriuresis after an additional small volume expansion (SVE). Thi s was systematically studied in anaesthetized Wistar rats prepared for clea rance studies of the left kidney and measurements of medullary blood flow ( MBF, laser-Doppler technique) and tissue electrical admittance (Y), an inde x of interstitial ion concentration. The rats were preinfused i.v. with 3 m L 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 mu mol min(-1) and urine flow (V ) from 12.0 +/- 2.3 to 24.3 +/- 5 .6 mu L min(-1) (P < 0.02). The same volume of whole blood increased UNaV f rom 5.0 +/- 1.4 to 8.7 +/- 1.7 mu mol min(-1) and V from 22.3 +/- 5.1 to 37 .4 +/- 5.9 mu L 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 o bserved after SVE. To examine if prostaglandins (PG) were involved in SVE n atriuresis, indomethacin (Indo), 5 mg kg(-1) or sodium meclophenamate (Mecl o), 7.5 mg kg(-1), were added to the injected 0.9% saline. Paradoxically, b oth PG synthesis inhibitors enhanced natriuresis to SVE. After Indo UNaV in creased from 2.0 +/- 0.6 to 7.6 +/- 1.3 mu mol min(-1), significantly more than after SVE alone (P < 0.001). At higher baseline UNaV, the increase wit h Meclo from 4.5 +/- 1.2 to 13.5 +/- 1.8 mu mol min(-1) was significantly h igher than after whole blood infusion (P < 0.001). MBF decreased and Y incr eased after both inhibitors. Further studies are required to explain the en hancement of natriuresis after blockade of PG synthesis.