Aortic Fibrosis, Induced by High Salt Intake in the Absence of Hypertensive Response, Is Reduced by a Monoclonal Antibody to Marinobufagenin

Yulia N. Grigorova, Ondrej Juhasz, Valentina Zernetkina, Kenneth W. Fishbein, Edward Lakatta, Olga V. Fedorova, Alexei Y. Bagrov

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Marinobufagenin (MBG) is an endogenous Na/K-ATPase inhibitor, a natriuretic and a vasoconstrictor. MBG is implicated in salt-sensitive hypertension, cardiac hypertrophy, and initiate the pro-fibrotic signaling. Previously it was demonstrated that immunoneutralization of an endogenous MBG by 3E9 anti-MBG-antibody (mAb) in vivo lowered blood pressure (BP) and reversed cardiac fibrosis in salt-sensitive, and in partially nephrectomized rats. In the present study, we investigated whether mAb alleviates vascular remodeling induced in normotensive rats on high salt intake. METHODS: Wistar rats (5 months old) received normal (CTRL; n = 8) or high salt intake (2% NaCl in drinking water) for 4 weeks (n = 16). Rats from the group on a high salt intake were administered vehicle (SALT; n = 8) or mAb (50 μg/kg) (SALT-AB; n = 8) during the last week of high salt diet. BP, erythrocyte Na/K-ATPase activity, levels of MBG in plasma and 24-hour urine, and sensitivity of aortic explants to the vasorelaxant effect of sodium nitroprusside (SNP) were measured. Aortic collagen abundance was determined immunohistochemically. RESULTS: In SALT vs. CTRL, heightened levels of MBG were associated with inhibition of erythrocyte Na/K-ATPase in the absence of BP changes. High salt intake was accompanied by a 2.5-fold increase in aortic collagen abundance and by a reduction of sensitivity of aortic explants to the vasorelaxant effect of SNP following endothelin-1-induced constriction. In the SALT-AB group, all NaCl-mediated effects were reversed by immunoneutralization of MBG. CONCLUSIONS: High salt intake in young normotensive rats can induce vascular fibrosis via pressure-independent/MBG-dependent mechanisms, and this remodeling is reduced by immunoneutralization of MBG.

Original languageEnglish (US)
Pages (from-to)641-646
Number of pages6
JournalAmerican Journal of Hypertension
Volume29
Issue number5
DOIs
StatePublished - May 1 2016
Externally publishedYes

Keywords

  • blood pressure
  • high salt intake
  • hypertention
  • marinobufagenin
  • monoclonal antibody
  • Na/K-ATPase
  • vascular fibrosis

ASJC Scopus subject areas

  • Internal Medicine

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