Eitle E, Harris P J, Morgan T O
Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.
Hypertension. 1994 Mar;23(3):358-63. doi: 10.1161/01.hyp.23.3.358.
Atrial natriuretic factor induces renal sodium excretion by several mechanisms, including inhibition of angiotensin II-stimulated sodium reabsorption in the proximal tubule. In most tissues, the action of atrial natriuretic factor involves generation of the intracellular second messenger, cyclic GMP, but in the proximal tubule the presence of this signal transduction pathway has remained controversial. We used intrarenal arterial infusion of iron oxide followed by enzymatic dispersion and magnetic separation to obtain suspensions of rabbit kidney cortex enriched with either glomeruli or proximal tubules. When suspensions enriched with proximal tubules or preparations of microdissected proximal tubules were incubated with atrial natriuretic factor (1 mumol/L), cyclic GMP concentrations increased significantly. Addition of angiotensin II (1 mumol/L) together with atrial natriuretic factor had no significant effect on the stimulation of cyclic GMP accumulation observed with atrial natriuretic factor alone. Neither atrial natriuretic factor nor angiotensin II altered intracellular concentrations of cyclic AMP in tubule-enriched suspensions or microdissected tubules. We conclude that cyclic GMP acts as a second messenger for atrial natriuretic factor in rabbit proximal tubule. However, we found no evidence to support the view that alterations in intracellular cyclic AMP levels are involved in the proximal tubular actions of angiotensin II and have not been able to demonstrate that interactions between cyclic AMP and cyclic GMP underlie the antagonistic effect of atrial natriuretic factor on angiotensin II-stimulated proximal sodium transport.
心房利钠因子通过多种机制诱导肾脏排钠，包括抑制近端小管中血管紧张素II刺激的钠重吸收。在大多数组织中，心房利钠因子的作用涉及细胞内第二信使环磷酸鸟苷（cGMP）的生成，但在近端小管中，这种信号转导途径的存在一直存在争议。我们通过肾内动脉注入氧化铁，随后进行酶分散和磁分离，以获得富含肾小球或近端小管的兔肾皮质悬浮液。当富含近端小管的悬浮液或显微解剖的近端小管制剂与心房利钠因子（1 μmol/L）一起孵育时，环磷酸鸟苷浓度显著增加。将血管紧张素II（1 μmol/L）与心房利钠因子一起添加，对单独使用心房利钠因子时观察到的环磷酸鸟苷积累的刺激没有显著影响。心房利钠因子和血管紧张素II均未改变富含小管的悬浮液或显微解剖小管中的细胞内环磷酸腺苷（cAMP）浓度。我们得出结论，环磷酸鸟苷在兔近端小管中作为心房利钠因子的第二信使。然而，我们没有发现证据支持细胞内环磷酸腺苷水平的改变参与血管紧张素II近端小管作用的观点，并且未能证明环磷酸腺苷和环磷酸鸟苷之间的相互作用是心房利钠因子对血管紧张素II刺激的近端钠转运产生拮抗作用的基础。
