Original Report: Laboratory Investigation

Effects of Resibufogenin in Experimental Hypertension
S. Danchuk^a, S. Sukhanov^b, D. Horvat^c, M.N. Uddin^c, J.B. Puschett^{a, c}

Sections of
^aNephrology and Hypertension and
^bCardiology, Department of Medicine, Tulane University School of Medicine, New Orleans, La., and
^cDivision of Nephrology and Hypertension, Department of Medicine, Texas A&M College of Medicine/Scott & White, Temple, Tex., USA

Address of Corresponding Author

Am J Nephrol 2008;28:8-13 (DOI: 10.1159/000108756)

  Key Words

• Marinobufagenin
• Experimental hypertension
• Volume expansion
• Angiotensinogen
• Resibufogenin

  Abstract

Background/Aims: There are two major pathophysiologic processes involved in the development of hypertension: (1) expanded extracellular fluid volume and (2) vasoconstriction. We have developed a model of preeclampsia in the rat, in which excessive volume expansion (VE) plays a role. These animals excrete increased amounts of the bufodienolide, marinobufagenin (MBG), even before their hypertension and proteinuria become established. Furthermore, their hypertension is corrected by administration of resibufogenin (RBG), a compound structurally similar to MBG. Method: We studied two models of experimental hypertension in the nonpregnant animal, produced either by deoxycorticosterone acetate (DOCA)-salt administration or by angiotensin infusion. Results: RBG administered to the DOCA-salt rats lowered blood pressure and reduced proteinuria in the VE animals, but had no affect on the rats infused with angiotensin. Furthermore, although the production of superoxide anion in the aortas of both groups of hypertensive rats was increased over control, RBG reduced these levels to normal in the VE (DOCA-salt) animals only. RBG had no effect in the angiotensin-infused rats. The urinary excretion of angiotensinogen did not rise in VE-mediated hypertension, but did increase in the angiotensin-infused rats. Conclusions: MBG plays an important role in the causation of hypertension in the VE rats, but not in the vasoconstrictive model. RBG is effective only in VE-mediated hypertension.

Copyright © 2007 S. Karger AG, Basel

  Author Contacts

Jules B. Puschett, MD
2401 South 31st Street, Room 407L
Temple, TX 76508 (USA)
Tel. +1 254 724 6791, Fax +1 254 724 8344
E-Mail jpuschett@swmail.sw.org

  Article Information

Received: June 26, 2007
Accepted: July 31, 2007
Published online: September 20, 2007
Number of Print Pages : 6
Number of Figures : 3, Number of Tables : 1, Number of References : 35