Open AccessCollecting Duct Nitric Oxide Synthase 1ß Activation Maintains Sodium Homeostasis During High Sodium Intake Through Suppression of Aldosterone and Renal Angiotensin II Pathways
Author(s) -
Hyndman Kelly A.,
Mironova Elena V.,
Giani Jorge F.,
Dugas Courtney,
Collins Jessika,
McDonough Alicia A.,
Stockand James D.,
Pollock Jennifer S.
Publication year - 2017
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.117.006896
Subject(s) - medicine , aldosterone , homeostasis , nitric oxide synthase , renin–angiotensin system , sodium , angiotensin ii , aldosterone synthase , endocrinology , nitric oxide , blood pressure , chemistry , organic chemistry
Background During high sodium intake, the renin‐angiotensin‐aldosterone system is downregulated and nitric oxide signaling is upregulated in order to remain in sodium balance. Recently, we showed that collecting duct nitric oxide synthase 1β is critical for fluid‐electrolyte balance and subsequently blood pressure regulation during high sodium feeding. The current study tested the hypothesis that high sodium activation of the collecting duct nitric oxide synthase 1β pathway is critical for maintaining sodium homeostasis and for the downregulation of the renin‐angiotensin‐aldosterone system–epithelial sodium channel axis. Methods and Results Male control and collecting duct nitric oxide synthase 1β knockout ( CDNOS 1 KO ) mice were placed on low, normal, and high sodium diets for 1 week. In response to the high sodium diet, plasma sodium was significantly increased in control mice and to a significantly greater level in CDNOS 1 KO mice. CDNOS 1 KO mice did not suppress plasma aldosterone in response to the high sodium diet, which may be partially explained by increased adrenal AT 1R expression. Plasma renin concentration was appropriately suppressed in both genotypes. Furthermore, CDNOS 1 KO mice had significantly higher intrarenal angiotensin II with high sodium diet, although intrarenal angiotensinogen levels and angiotensin‐converting enzyme activity were similar between knockout mice and controls. In agreement with inappropriate renin‐angiotensin‐aldosterone system activation in the CDNOS 1 KO mice on a high sodium diet, epithelial sodium channel activity and sodium transporter abundance were significantly higher compared with controls. Conclusions These data demonstrate that high sodium activation of collecting duct nitric oxide synthase 1β signaling induces suppression of systemic and intrarenal renin‐angiotensin‐aldosterone system, thereby modulating epithelial sodium channel and other sodium transporter abundance and activity to maintain sodium homeostasis.