Marleau S, Ong H, De Léan A, du Souich P
Faculté de Pharmacie, Université de Montréal, Québec, Canada.
J Pharmacol Exp Ther. 1989 Oct;251(1):328-33.
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.
在清醒兔中记录了心房利钠因子(ANF)、大鼠ANF(99 - 126)的动力学和动态变化。静脉注射高达300 ng/kg的免疫反应性ANF(IR-ANF)后,其动力学呈一级反应。与静脉注射相比,持续输注ANF导致IR-ANF的全身清除率显著降低,对于81±8 ng/min/kg(×140分钟)和126±6 ng/min/kg(×480分钟)的输注速率,全身清除率分别从132降至59和70 ml/min/kg(P<0.0001);然而,ANF的分布未受影响。在输注ANF期间,平均动脉压和肾血浆流量显著降低,而对水和钠参数的肾脏排泄影响最小。血流动力学变化伴随着血浆肾素活性的反弹增加。得出结论,在持续输注后,IR-ANF的动力学呈零级反应,这是由于ANF全身清除率下降所致,并且在该动物模型中,在所使用的剂量下,这种肽仅引发血流动力学效应,可能与反调节机制的激活有关。