Abstract
We have recently reported that type A intercalated cells of the collecting duct secrete Na+ by a mechanism coupling the basolateral type 1 Na+-K+-2Cl- cotransporter with apical type 2 H+-K+-ATPase (HKA2) functioning under its Na+/K+ exchange mode. The first aim of the present study was to evaluate whether this secretory pathway is a target of atrial natriuretic peptide (ANP). Despite hyperaldosteronemia, metabolic acidosis is not associated with Na+ retention. The second aim of the present study was to evaluate whether ANP-induced stimulation of Na+ secretion by type A intercalated cells might account for mineralocorticoid escape during metabolic acidosis. In Xenopus oocytes expressing HKA2, cGMP, the second messenger of ANP, increased the membrane expression, activity, and Na+-transporting rate of HKA2. Feeding mice with a NH4Cl-enriched diet increased urinary excretion of aldosterone and induced a transient Na+ retention that reversed within 3 days. At that time, expression of ANP mRNA in the collecting duct and urinary excretion of cGMP were increased. Reversion of Na+ retention was prevented by treatment with an inhibitor of ANP receptors and was absent in HKA2-null mice. In conclusion, paracrine stimulation of HKA2 by ANP is responsible for the escape of the Na+-retaining effect of aldosterone during metabolic acidosis.
Highlights
Since the work of Guyton et al [12], kidneys have been considered as the main effectors of the regulation of volemia and blood pressure owing to their role in the maintenance of hydroelectrolytical homeostasis
Our results suggest that atrial natriuretic peptide (ANP)-mediated activation of HKA2 and of Naϩ secretion along the collecting duct (CCD) accounts for the maintenance of Naϩ balance during metabolic acidosis
Our results show that ANP and its intracellular second messenger, cGMP, stimulate membrane expression and activity of nongastric Hϩ-Kϩ-ATPase and increase the Naϩ/Kϩ over Hϩ/Kϩ functioning ratio of the pump
Summary
Since the work of Guyton et al [12], kidneys have been considered as the main effectors of the regulation of volemia and blood pressure owing to their role in the maintenance of hydroelectrolytical homeostasis. Intercalated cells have been classically considered as responsible for the maintenance of acid-base balance, but recent work has shown that BICs reabsorb NaCl [20], whereas AICs secrete it [23]. The net transport of Naϩ along the CNT/CCD is the algebraic sum of its reabsorption via PCs and BICs and its secretion via AICs, and the fine tuning of this transport results from the coordinated control of the transport activities of these three cell types. Control of Naϩ transport in the distal nephron relies on a complex system of endocrine and paracrine factors and of neuromediators [9], most of which act together on Naϩ transport in the distal nephron and on vascular and/or cardiac reactivity They are either antinatriuretic/vasoconstrictor factors, mainly represented by vasopressin and the renin-angiotensin-aldosterone system, or the more numerous natriuretic/
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
