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High Salt Activation of Collecting Duct‐Derived Nitric Oxide Synthase Suppresses the Renin‐Angiotensin‐Aldosterone (RAAS) System
Author(s) -
Pollock Jennifer S,
Pollock David M,
Dugas Courtney,
Hyndman Kelly A
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.962.5
Subject(s) - endocrinology , medicine , aldosterone , chemistry , excretion , nitric oxide , renin–angiotensin system , plasma renin activity , homeostasis , nitric oxide synthase , angiotensin ii , blood pressure , biology
We reported that collecting duct nitric oxide synthase‐1 knockout (CDNOS1KO) mice display a salt‐sensitive blood pressure phenotype with reduced Na excretion in response to a high salt (HS) diet. To further delineate the relationship of CD NOS1 activation and Na homeostasis, we designed experiments to test the hypothesis that HS induced activation of CD NOS1 functions to suppress the RAAS. Adult male CDNOS1KO and flox control mice were placed on normal (NS) or HS diet for 7 days (NS: 0.4% NaCl, HS: 4% NaCl). NO production in isolated CD preparations from the CDNOS1KO mice was significantly reduced compared to control mice on NS (0.5±0.09 vs 1.0±0.03 pmol/mg pr/h, p< 0.05) and HS (1.5±0.3 vs 2.8±0.2 pmol/mg pr/h, p<0.05). HS induced urinary NOx excretion was also significantly reduced in CDNOS1KO mice by >50% compared to control. HS induced significantly higher plasma Na levels in CDNOS1KO mice (+8 mEq/L; p<0.05) compared to control mice. Plasma K levels were similar in NS and HS in both genotypes. HS significantly reduced plasma aldosterone (532.6±93.0 vs 55.6±10.4 pg/ml) and urinary aldosterone excretion in the control mice (4.2±0.7 vs 1.7±0.4 ng/day), however this reduction was abolished in CDNOS1KO mice (402.0±68 vs 276.5±55 pg/ml; 4.1±0.8 vs 3.7±0.7 ng/day). Plasma renin concentration was similar in both genotypes with HS intake yet blood pressure was significantly higher in CDNOS1KO mice, thus CDNOS1KO mice display an in appropriately high level of plasma renin with HS. Furthermore, renal renin expression was enhanced in CDNOS1KO mice compared to controls. These data demonstrate that loss of CD NOS1 facilitates sustained elevations in plasma Na levels as well as plasma and intra‐renal renin that further enhances activation of aldosterone. These findings indicate that CD NO, especially NOS1‐derived, is vital for systemic Na homeostasis under HS conditions. Support or Funding Information NIH P01HL95499