To examine whether hemodynamic and natriuretic effects of alpha-human atrial natriuretic peptide (ANP) were modulated by calcium (Ca) ion, Ca entry blocker nifedipine (Nif) was administered prior to ANP infusion in anesthetized rabbits. We also examined the effect of Nif and ANP on the renal kallikrein-kinin system. Both Nif. (1.0 micrograms/kg/min) and ANP (50 ng/kg/min) increased urinary sodium excretion (UNaV) without change in renal hemodynamics, although mean arterial pressure (MAP) decreased. Fractional excretion of sodium (FENa) was also increased significantly by both Nif and ANP. Nif infusion alone decreased MAP, the additional infusion of ANP on Nif pretreatment induced a further decrease in MAP and caused an increase in UNaV and FENa without renal hemodynamics changes. The administration of ANP increased urinary excretion of kallikrein and kinin. The additional infusion of ANP on Nif pretreatment induced a further increase in urinary kallikrein and kinin. These results suggest that Ca ion does not participate in ANP-induced natriuresis. Renal kallikrein-kinin may partly involve in natriuresis induced by ANP.