AIMS: To investigate whether blockade of calcium channels (CCs) or Angiotensin II Type 1 receptors 1 (AT1R) modulates renal responses to nitric oxide synthesis inhibition (NOSI) in humans. METHODS: Fourteen sodium replete healthy volunteers underwent 90 minute infusions of 3.0 μg.kg.min-1 NG-nitro-L-arginine methylester (L-NAME), on 3 occasions, preceded by 3 days of either placebo (PL), 10 mg Manidipine (MANI), or 50 mg losartan (LOS). At each phase, mean arterial pressure (MAP), glomerular filtration rate (GFR, inulin), renal blood flow (RBF, p-aminohippurate), urinary sodium (UNaV) and 8-isoprostane (U8-iso-PGF2αV - an oxidative stress marker) were measured. RESULTS: With PL+L-NAME, the following changes were observed: +6 % MAP (p<0.005 vs. baseline), -10 % GFR, -20 % RBF, -49% UNaV (p<0.001) and +120% U8-iso-PGF2αV (p<0.01). In contrast, MAP did not increase during LOS+L-NAME or MANI+L-NAME (p>0.05 vs. baseline), while renal changes were the same during LOS+L-NAME vs. PL+L-NAME (ANOVA p>0.05). However, during MANI+L-NAME, changes vs. baseline in GFR (-6 %), RBF (-12%) and UNaV (-34%) were blunted vs. PL+L-NAME and LOS+L-NAME (p<0.005), and the rise in U8-iso-PGF2αV was almost abolished (+37%, p>0.05 vs. baseline; p<0.01 vs. PL+L-NAME or LOS+L-NAME). CONCLUSION: Since MANI blunted L-NAME-induced renal hemodynamic changes, CCs participate in the renal responses to NOSI in healthy, sodium-replete humans, independent of changes in MAP and without apparent contribution of the AT1R. Because the rise in U8-iso-PGF2αV was essentially prevented during MANI+L-NAME, CC blockade may oppose the renal effects of NOSI in part by counteracting oxidative stress responses to acutely impaired renal NO bioavailability.