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

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

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Faculty of Medicine and Health Science, Universiti Sultan Zainal Abidin (UniSZA), Kota Campus, Jalan Sultan Mahmud, Kuala Terengganu, Terengganu Darul Iman, 20400, Malaysia. Electronic address:
Faculty of Medicine,Universiti Teknologi MARA, 47100, Sg Buloh, Selangor, Malaysia; Institute of Medical and Molecular Biotechnology, Universiti Teknologi MARA, 47100, Sg Buloh, Selangor, Malaysia.


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.


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

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