The effect of salt on renal damage in eNOS-deficient mice.
African Americans have an increased incidence of end-stage renal disease and are characterized as having reduced bioavailability of nitric oxide and salt-sensitivity. We propose that endothelial nitric oxide synthase (eNOS) knockout mice (eNOS(-/-)) are a suitable model of hypertension-associated renal injury as seen in African Americans. Therefore, the purpose of this study was to determine whether older eNOS(-/-) mice have hypertension-associated renal injury and if dietary salt modulates this injury. Six-month-old eNOS(-/-) mice were placed on 0.12%, 0.45% or 8% NaCl diet for 8 weeks and blood pressure measured weekly; kidneys were collected for pathology evaluation and scoring at the end of the 8-week period. Mice deficient of eNOS were hypertensive at baseline compared with control mice in all three groups (128+/-3 vs. 112+/-3, P<0.05). Blood pressure was significantly elevated from baseline in eNOS(-/-) on 0.45 and 8% salt diets (P<0.02). The composite renal pathology scores for eNOS(-/-) mice were significantly greater than wild-type mice, indicating high salt intake exacerbates the injury (P<0.001 vs. normal salt diet). eNOS(-/-) mice may be used as a model of salt-induced and hypertension-associated renal injury as seen in African Americans.
Daumerie
Geraldine
G
Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA.
Bridges
Lakeesha
L
Yancey
Sadiqa
S
Davis
Wendell
W
Huang
Paul
P
Loscalzo
Joseph
J
Pointer
Mildred A
MA
D001741:Black or African American; D000818:Animals; D001794:Blood Pressure; D006332:Cardiomegaly / Q000209:etiology; D006801:Humans; D006973:Hypertension / Q000473:pathology*; D007668:Kidney / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency / Q000502:physiology*; D009929:Organ Size; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*
D017673:Sodium Chloride, Dietary; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse