This study investigated the role of nitric oxide (NO) and superoxide anions in modulating the renal nerve-dependent increases in proximal tubular fluid reabsorption (Jva). Renal nerve stimulation at 0.75 and 1.0 Hz (15 V, 0.2 ms) in anaesthetized Wistar rats had no effect on glomerular filtration rate but decreased urine flow and sodium excretion in a frequency-related manner, reaching 39 and 49% at 1.0 Hz, respectively (P < 0.01) and increased Jva by 11 and 31% (P < 0.01). In the stroke prone spontaneously hypertensive rats (SHRSP), basal mean blood pressure was higher (123 +/- 2 versus 99 +/- 2 mmHg, P < 0.001), glomerular filtration rate, urine flow, sodium excretion and proximal tubular fluid reabsorption (Jva) were lower (all P < 0.001) than in the Wistar rats. Renal nerve stimulation in the SHRSP did not change glomerular filtration rate but decreased urine flow, and sodium excretion by 18 and 34% (P < 0.05) at 1.0 Hz which was less (P < 0.05) than that in the Wistar rats. Under these conditions, Jva was increased at 0.75 Hz by 27%, and to a comparable extent at 1.0 Hz, which was a pattern very different from the frequency related rises reported in the Wistar rats. In the SHRSP, intratubular Nomega-nitro-L-arginine methyl ester (L-NAME) had no effect on baseline Jva or the pattern of response to renal nerve stimulation which contrasted with earlier reports in the Wistar rat. Intraluminal superoxide dismutase (SOD) had no effect on basal Jva in the Wistar rats but increased it in the SHRSP (P < 0.05) while the pattern of change in Jva during nerve stimulation was unaltered in both rat strains. By contrast, in the SHRSP, intraluminal sodium nitroprusside (SNP) resulted in a frequency related increase in Jva comparable to that obtained in the vehicle treated Wistar rats. These data suggest that in the hypertensive rats, superoxide anion production is raised which depresses Jva and interacts with NO preventing a normal Jva response to renal nerve stimulation.