Disposition and dynamics of atrial natriuretic factor in conscious rabbits

The kinetics and dynamics of atrial natriuretic factor (ANF), rat ANF(99-126), were documented in conscious rabbits. The kinetics of immunoreactive ANF (IR-ANF) were first-order after a bolus of up to 300 ng/kg. Compared to the bolus, prolonged infusion of ANF produced a significant reduction in the systemic clearance of IR-ANF, from 132 to 59 and 70 ml/min/kg (P less than .0001) for the 81 +/- 8 ng/min/kg (x140 min) and 126 +/- 6 ng/min/kg (x480 min) infusion rates, respectively; however, the distribution of ANF was not affected. During the infusion of ANF, there was a marked decrease in mean arterial pressure and renal plasma flow, whereas the effects on renal excretion of water and sodium parameters were minimal. The change in hemodynamics was accompanied by a rebound increase in plasma renin activity. It is concluded that the kinetics of IR-ANF are zero-order after a prolonged infusion, secondary to a fall in the systemic clearance of ANF and that in this animal model, and at the doses used, this peptide only elicited hemodynamic effects, possibly related to the activation of counter-regulatory mechanisms.