ANP-stimulated Na⁺ secretion in the collecting duct prevents Na⁺ retention in the renal adaptation to acid load

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.

Natriuretic Peptides as Biomarkers: Narrative Review and Considerations in Cardiovascular and Respiratory Dysfunctions

“…Tissues other than cardiomyocytes, such as the uterus, spleen, thyroid, and prostate, also produce ANP and BNP [24]. Hormones such as endothelin, angiotensin, and arginine-vasopressin (AVP) stimulate ANP release, as do water immersion and head-down tilt [25][26][27][28][29][30]. It has been described that, as well as ANP, hormones, such as catecholamines, angiotensin II, and endothelin, and disease-associated conditions, such as hypoxia, enhance the secretion of NT-proBNP [31,32].…”

“…NPR-A stimulation in the kidneys by ANP increases natriuresis by decreasing the open probability of epithelial sodium channels (ENaCs) [46]. In addition, ANP is a key player in the aldosterone escape phenomenon [26], a natriuretic compensatory mechanism triggered by extracellular fluid volume expansion in response to the sodium-retaining effects of aldosterone [47].…”