title: Increased salt-sensitivity in endothelial nitric oxide synthase-knockout mice.
abstract: BACKGROUND
  Although impaired nitric oxide production contributes importantly to salt-sensitivity, the role of the endothelial isoform of nitric oxide synthase (eNOS) has received little attention. In the present study we compared the effects of a high-salt diet on the blood pressure response of eNOS knockout (eNOS-/-) and control (eNOS+/+) mice.
  
  
  METHODS
  Mean arterial pressure (MAP), heart rate, pulse pressure, and activity levels were recorded by telemetry in mice fed a regular-salt diet (0.7% NaCl) followed by 6 weeks on either a high-salt (8% NaCl) or regular-salt diet.
  
  
  RESULTS
  The eNOS-/- mice exhibited a 15% increase in MAP and a 2- to 2.5-fold increase in salt-sensitivity relative to the control strain. Salt-induced increases in MAP were well sustained in eNOS-/-, whereas in eNOS+/+ the initial increase was biphasic. The effects of salt on MAP were particularly pronounced during locomotor activity, during the dark phase, and at the peak levels of MAP recorded over the course of the day. The high-salt diet also led to a transient increase in the proportion of time spent active. Levels of heart rate and pulse pressure were relatively unaffected by the high-salt diet.
  
  
  CONCLUSIONS
  The eNOS-/- mice exhibit an increased blood pressure response to a high-salt diet. This finding suggests that eNOS normally provides an important contribution to the body's adaptation to a salt load and that reduced production of NO by eNOS may promote salt-sensitivity and salt-induced hypertension.
authors.affiliation: Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
authors.forename: Allison M
authors.initials: AM
authors.lastname: Leonard
authors.forename: Linda L
authors.initials: LL
authors.lastname: Chafe
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Montani
authors.forename: Bruce N
authors.initials: BN
authors.lastname: Van Vliet
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002940:Circadian Rhythm; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*; D013686:Telemetry; D013997:Time Factors
chemical_list: D017673:Sodium Chloride, Dietary; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse