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

American Journal of Hypertension
Yulia N GrigorovaAlexei Y Bagrov

Abstract

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. 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. In SALT vs. CTRL, heightened levels of MBG were associated with inhibition of erythrocyte Na/K-ATPase in the absence of BP changes. High...Continue Reading

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Citations

Jun 20, 2017·Current Medicinal Chemistry·Sergei N OrlovNickolai O Dulin
Aug 16, 2019·Journal of Cardiovascular Pharmacology·Olga V FedorovaAlexei Y Bagrov
Oct 18, 2018·International Journal of Molecular Sciences·Yulia N GrigorovaOlga V Fedorova
Feb 2, 2019·International Journal of Molecular Sciences·Aneta PaczulaGrzegorz Piecha
Sep 12, 2018·International Journal of Molecular Sciences·Fatimah K KhalafDavid J Kennedy
Aug 28, 2021·Life·Natalia Słabiak-Błaż, Grzegorz Piecha

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