title: ACE2 activation by xanthenone prevents leptin-induced increases in blood pressure and proteinuria during pregnancy in Sprague-Dawley rats.
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.
authors.affiliation: 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: hishamibrahim69@gmail.com.
authors.forename: Hisham Saleh
authors.initials: HS
authors.lastname: Ibrahim
authors.affiliation: 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.
authors.forename: Gabrielle Ruth Anisah
authors.initials: GR
authors.lastname: Froemming
authors.affiliation: 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.
authors.forename: Effat
authors.initials: E
authors.lastname: Omar
authors.affiliation: 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.
authors.forename: Harbindar Jeet
authors.initials: HJ
authors.lastname: Singh
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D019040:E-Selectin / Q000097:blood; D019332:Endothelin-1 / Q000097:blood; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D020738:Leptin / Q000009:adverse effects*; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced / Q000517:prevention & control*; D011507:Proteinuria / Q000139:chemically induced / Q000150:complications / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014966:Xanthenes / Q000494:pharmacology*
chemical_list: D019040:E-Selectin; D019332:Endothelin-1; D020738:Leptin; D014966:Xanthenes; D018799:Intercellular Adhesion Molecule-1; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2
keywords: ACE2; Blood pressure; E-selectin; Endothelial activation; Endothelin-1; ICAM-1; Leptin; Proteinuria