Nitric oxide (NO) and superoxide anions (O2.–) are generated in significant amounts in the kidney, especially in the medulla. The level of O2.- is determined by the activity of superoxide dismutase (SOD) under normal conditions and, due to O2.- degrading NO, this will affect basal levels of renal haemodynamics as well as neurally mediated vasoconstriction. This study investigated whether scavenging of O2.- modulated renal sympathetic nerve (RSN)-induced reductions in renal cortical and medullary blood flow in normotensive and hypertensive rats. Four groups (n= 9) of male Wistar and stroke prone spontaneously hypertensive rats (SHRSP), 250-300 g, were anaesthetised with 1 ml i.p. chloralose/urethane (16.5/250 mg/ml, respectively). The right femoral vein and artery were cannulated for infusion of saline (154 mM NaCl) at 3 ml/h, anaesthetic supplementation (0.5 ml every 30 min), and measurement of arterial blood pressure (BP). The left kidney was exposed via a flank incision, placed in a holder and a small cannula was inserted 4.5 mm into the kidney for intramedullary (i.m.) infusion of saline or drugs at 0.6-1.0 ml/h. Two Laser-Doppler microprobes were inserted 1.5 and 4.0 mm into the kidney to measure cortical (CP) and medullary (MP) blood perfusion, respectively, in perfusion units (PU). Bipolar stainless steel electrodes were connected to a stimulator and applied to the area in which the renal nerves were usually located. After 90min, baseline values were taken, the stimulation was performed (15V, 2 ms) for 1 min at frequencies of 0.5, 1, 2, 4, 6 and 8 Hz with 5 min rest periods, then either vehicle or tempol (a SOD mimetic) was infused at 30µmol/kg/min i.m. for 90 min and the stimulation protocol was repeated. Data±SEM were subjected to Student’s t test and significance taken at P<0.05. The animals were killed with an anaesthetic overdose. In Wistar rats, base line levels of BP, MP and CP were 108±2 mmHg, 78±11 PU and 142±21 PU, respectively, and for SHRSP BP was 130±5 mmHg, MP was 73±9 PU and CP was 112±11 PU. RSN stimulation in the Wistar rats caused a frequency-related reduction in MP and CP of 37% and 74%, respectively (both P <0.05), at 8 Hz. After the infusion of tempol MP, but not CP, increased from 108±14 to 125±16 PU (P<0.05), the nerve-induced reductions in MP and CP were 30% and 52%, respectively (both P< 0.05), the latter being smaller (P<0.05) than in the absence of drug. In SHRSP, the RSN stimulation frequency-related decreases in MP and CP were 19% and 51%, respectively (both P<0.05) at 8 Hz, and tempol infusion increased MP, but not CP, from 61±8 to 86±10 PU (P<0.05), but the magnitudes of the renal nerve-induced responses were unchanged during tempol infusion. These results indicate that the RSN caused larger reductions in CP than MP in both Wistar and SHRSP, although the responses were larger in the Wistar rats. Scavenging of O2.- with tempol blunted the MP and CP responses, possibly as a result of greater NO availability buffering the neural vasoconstrictions. These potential relationships appeared disturbed in the SHRSP.