Renal nerves play an important role in the setting of the sensitivity of the tubuloglomerular feedback (TGF) mechanism. We recently reported a time-dependent resetting of TGF to a lower sensitivity 3-4 h after acute unilateral renal denervation (aDNX). This effect persisted after 1 week, but was then less pronounced. To determine whether normal TGF sensitivity could be restored in aDNX kidneys by low-frequency renal nerve stimulation (RNS), the following experiments were performed. Rats with aDNX were prepared for micropuncture. In one experimental group proximal tubular free flow (Pt) and stop flow pressures (Psf) were measured during RNS at frequencies of 2, 4 and 6 Hz. In another series of experiments the TGF sensitivity was evaluated from the Psf responses at different loop perfusion rates after 20 min of RNS at a frequency of 2 Hz. The maximal drop in Psf (delta Psf) and the tubular flow rate at which half the maximal response in delta Psf was observed (turning point, TP), were recorded. At RNS frequencies of 2, 4 and 6 Hz, Pt decreased from the control level of 14.1 +/- 0.8-13.1 +/- 1.0, 12.4 +/- 1.1 and 11.2 +/- 0.8 mmHg (decrease 21%, P < 0.05), respectively, while at zero perfusion and during RNS at 2 and 4 Hz Psf decreased from 42.5 +/- 1.6 to 38.2 +/- 1.4 and 32.8 +/- 4.3 mmHg (decrease 23%, P < 0.05), respectively. The TGF characteristics were found to be reset from the normal sensitivity with TP of 19.0 +/- 1.1 nL min-1 and delta Psf of 8.7 +/- 0.9 mmHg to TP of 28.3 +/- 2.4 nL min-1 (increase 49%, P < 0.05) and delta Psf of 5.8 +/- 1.2 mmHg (decrease 33%) after aDNX. After 20 min of RNS at 2 Hz TP was normalized and delta Psf was 33% higher. Thus the present findings indicate that the resetting of the TGF sensitivity that occurred 2-3 h after aDNX could be partially restored by 20 min of RNS at a frequency of 2 Hz. These results imply that renal nerves have an important impact on the setting of the sensitivity of the TGF mechanism.