ACE2 activation by xanthenone prevents leptin-induced increases in blood pressure and proteinuria during pregnancy in Sprague-Dawley rats

Reprod Toxicol. 2014 Nov:49:155-61. doi: 10.1016/j.reprotox.2014.08.006. Epub 2014 Sep 6.

Abstract

This study investigates the effect of ACE2 activation on leptin-induced changes in systolic blood pressure (SBP), proteinuria, endothelial activation and ACE2 expression during pregnancy in Sprague-Dawley rats. Pregnant rats were given subcutaneous injection of either saline, or leptin, or leptin plus xanthenone (ACE2 activator), or xanthenone (XTN) alone. SBP, serum ACE, ACE2, endothelin-1, E-selectin and ICAM-1 levels were estimated; also their gene expressions were determined in the kidney and aorta respectively. Compared to control, SBP was higher in the leptin-only treated group (P<0.001) and lower in rats treated with xanthenone alone (P<0.01). Proteinuria, markers of endothelial activation were significantly higher than controls in leptin-only treated rats (P<0.05). ACE2 activity and expression were lower in leptin-only treated rats when compared to controls (P<0.05). It seems, leptin administration during pregnancy significantly increases SBP, proteinuria, endothelial activation, but decreases ACE2 level and expression. These effects are prevented by concurrent administration of xanthenone.

Keywords: ACE2; Blood pressure; E-selectin; Endothelial activation; Endothelin-1; ICAM-1; Leptin; Proteinuria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Blood Pressure / drug effects*
  • E-Selectin / blood
  • Endothelin-1 / blood
  • Enzyme Activation / drug effects
  • Female
  • Intercellular Adhesion Molecule-1 / blood
  • Leptin / adverse effects*
  • Peptidyl-Dipeptidase A / drug effects*
  • Peptidyl-Dipeptidase A / metabolism
  • Pregnancy
  • Pregnancy Complications / chemically induced
  • Pregnancy Complications / prevention & control*
  • Proteinuria / chemically induced
  • Proteinuria / complications
  • Proteinuria / prevention & control*
  • Rats
  • Rats, Sprague-Dawley
  • Xanthenes / pharmacology*

Substances

  • E-Selectin
  • Endothelin-1
  • Leptin
  • Xanthenes
  • Intercellular Adhesion Molecule-1
  • Peptidyl-Dipeptidase A
  • Ace2 protein, rat
  • Angiotensin-Converting Enzyme 2