title: Endogenous ouabain and the renin-angiotensin-aldosterone system: distinct effects on Na handling and blood pressure in human hypertension.
abstract: OBJECTIVE
  To evaluate whether the renin-angiotensin-aldosterone system (RAAS) and endogenous ouabain system differently affect renal Na handling and blood pressure.
  
  
  METHODS
  Three hundred and one patients in whom we compared blood pressure, and renal Na tubular reabsorption in the basal condition and 2 h (T120) after saline infusion.
  
  
  RESULTS
  Following multivariate-adjusted linear and quartiles analysis, baseline mean blood pressure (MBP) was significantly higher (113.7 ± 1.33 mmHg) in the fourth versus the first endogenous ouabain quartile (103.8 ± 1.04 mmHg) and the trend across the quartiles was highly significant (β = 0.23, P = 3.53e-04). In contrast, an inverse relationship was present in the renin activity (PRA) quartiles with MBP highest in the first (112.5 ± 1.26) and lowest in the fourth PRA quartile (107.6 ± 1.48, P = 0.039). Following an acute saline load, changes in MBP and the slope of the pressure-natriuresis relationship were inversely related across the PRA quartiles. The fractional excretion of sodium (FENa) showed a negative linear trend going from the first to the third endogenous ouabain quartiles (2.35 ± 0.17 and 1.90 ± 0.14%, P = 0.05). Patients in the fourth endogenous ouabain quartile (>323 pmol/l) showed increased FENa T120 (2.78 ± 0.18%, P < 0.01) and increased Na tubular rejection fraction (P = 0.007) after Na load. After the saline load, there was a biphasic relationship between plasma endogenous ouabain and FENa favoring Na retention at low endogenous ouabain and Na excretion at high endogenous ouabain levels.
  
  
  CONCLUSIONS
  The RAAS and endogenous ouabain system are two independent and complementary systems having an inverse (RAAS) or a direct (endogenous ouabain system) relationship with hemodynamic parameters.
authors.affiliation: Nephrology, and Dialysis San Raffaele Scientific Institute, Università Vita-Salute San Raffaele, Milan, Italy. manunta.paolo@hsr.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Manunta
authors.forename: John M
authors.initials: JM
authors.lastname: Hamlyn
authors.forename: Marco
authors.initials: M
authors.lastname: Simonini
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Messaggio
authors.forename: Chiara
authors.initials: C
authors.lastname: Lanzani
authors.forename: Maria
authors.initials: M
authors.lastname: Bracale
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Argiolas
authors.forename: Nunzia
authors.initials: N
authors.lastname: Casamassima
authors.forename: Elena
authors.initials: E
authors.lastname: Brioni
authors.forename: Nicola
authors.initials: N
authors.lastname: Glorioso
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bianchi
mesh_terms: D000328:Adult; D000450:Aldosterone / Q000097:blood; D001794:Blood Pressure / Q000502:physiology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D007684:Kidney Tubules / Q000503:physiopathology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000502:physiology; D010042:Ouabain / Q000097:blood*; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology*; D012964:Sodium / Q000097:blood / Q000378:metabolism
chemical_list: D000450:Aldosterone; D010042:Ouabain; D012964:Sodium; D012083:Renin