Widimsky J, Kuchel O, Debinski W, Du Souich P
Laboratory of the Autonomic Nervous System, Clinical Research Institute of Montreal, Hotel-Dieu Hospital, Québec, Canada.
Proc Soc Exp Biol Med. 1991 Oct;198(1):555-60. doi: 10.3181/00379727-198-43288.
We have reported a paradoxical plasma atrial natriuretic factor (ANF) decline following prolonged high salt intake that was attributed to an increased tissue uptake of circulating ANF, leading to its augmented distribution volume (Vas) and metabolic clearance rate (MCR) as compared with control rats on a standard diet. To explore this phenomenon further, we evaluated possible chronic salt-loading-induced changes in ANF clearance (C-ANF) receptors, which appear to play a major role in ANF removal from the circulation. We studied changes in plasma [125I]ANF(1-28) and its pharmacokinetics after preoccupation of C-ANF receptors by its specific ligand, C-ANF(4-23), in high-salt-treated rats and their controls. Following C-ANF(4-23) administration, we detected significantly higher circulating [125I]ANF levels throughout the study period (8 min) in high-salt-fed rats compared with the controls (280-470% vs 100-215% increase of basal values, P less than 0.05). C-ANF(4-23) infusion caused a significantly greater decrease of the metabolic clearance rate and distribution volume of [125I]ANF in high-salt-fed rats than in control animals (74 +/- 6% vs 41 +/- 6% and 75 +/- 4% vs 50 +/- 5% of basal values, respectively; P less than 0.05). These data suggest that a prolonged high salt diet may increase the availability of C-ANF receptors and, through this mechanism, may negatively modulate plasma ANF concentrations. C-ANF receptors may thus fulfill a regulatory function on circulating ANF during prolonged salt loading in rats.
我们曾报道，长期高盐摄入后会出现矛盾的血浆心房利钠因子（ANF）下降情况，这归因于循环中ANF的组织摄取增加，导致与标准饮食的对照大鼠相比，其分布容积（Vas）和代谢清除率（MCR）增大。为进一步探究这一现象，我们评估了慢性高盐负荷可能导致的ANF清除（C-ANF）受体变化，该受体似乎在ANF从循环中清除过程中起主要作用。我们研究了在高盐处理大鼠及其对照中，其特异性配体C-ANF(4 - 23)占据C-ANF受体后血浆[125I]ANF(1 - 28)的变化及其药代动力学。给予C-ANF(4 - 23)后，我们发现在整个研究期间（8分钟），高盐喂养大鼠的循环[125I]ANF水平显著高于对照大鼠（基础值增加280 - 470% vs 100 - 215%，P小于0.05）。与对照动物相比，C-ANF(4 - 23)输注导致高盐喂养大鼠中[125I]ANF的代谢清除率和分布容积下降幅度显著更大（分别为基础值的74±6% vs 41±6%和75±4% vs 50±5%；P小于0.05）。这些数据表明，长期高盐饮食可能会增加C-ANF受体的可利用性，并通过这一机制对血浆ANF浓度产生负调节作用。因此，在大鼠长期盐负荷期间，C-ANF受体可能对循环中的ANF发挥调节功能。
