The present study was conducted to determine whether exogenous angiotensin II (Ang II) may increase the renal interstitial fluid concentrations of NO2/NO3 (NOx) and cyclic guanosine monophosphate (cGMP) concomitantly and which Ang II receptor subtypes may induce these changes in anesthetized rats, using a microdialysis method. Ang II (50 ng/kg per min, i.v.) significantly increased mean blood pressure (MBP), extraction rates of renal interstitial NOx from 23.9+/-1.0 to 31.2+/-1.9 pmol/min, and cGMP from 4.1+/-0.3 to 6.4+/-0.5 fmol/min, and decreased renal blood flow (RBF). The AT1-receptor antagonist CV11974 alone significantly increased RBF, but did not alter MBP, renal interstitial concentrations of NOx and cGMP. A superimposition of Ang II on CV11974 did not affect MBP and RBF, but significantly increased renal interstitial concentrations of NOx and cGMP. The AT2-receptor antagonist PD123319 alone did not change any of the parameters. However, superimposition of Ang II on PD123319 increased MBP and decreased RBF without any effects on renal interstitial concentrations of NOx and cGMP. These results suggest that Ang II stimulates NO production via the AT2-receptor in the kidney.