Effect of exogenous leptin on blood pressure, urinary protein excresion, endothelial activation and Ace2 expression during pregnancy in the rat / Dr Hisham S Ibrahim Al-Shaikhli

Ibrahim Al-Shaikhli, Hisham S (2014) Effect of exogenous leptin on blood pressure, urinary protein excresion, endothelial activation and Ace2 expression during pregnancy in the rat / Dr Hisham S Ibrahim Al-Shaikhli. PhD thesis, Universiti Teknologi MARA.

Abstract

Raised leptin levels have been reported in placentae and serum of women with elevated blood pressure and proteinuria during pregnancy. The role of leptin in this however remains unclear. ACE2 is a new member in RAAS, which is reported to have hypotensive and anti-inflammatory effect and its suppression leads to increased blood pressure and endothelial activation. Therefore, this study investigated the effect of leptin and xanthenone (ACE2 activator) administration on systolic blood pressure (SBP), proteinuria and serum markers of endothelial activation during pregnancy in Sprague-Dawley rats. Eighty female Sprague-Dawley rats, aged 12-13 weeks were randomised into 10 groups, Group 1 acted as a control non-pregnant group and given saline (NSNP). Group 2, control pregnant rats, was given saline (NSP), group 3 was given 60 ug / kg /day of leptin starting from the 1st day of pregnancy (LD1-60), group 4, was given 60 ug / kg /day ofleptin starting from the 10th day of pregnancy (LDI0), group 5, given leptin from day 16 of pregnancy (LD16). Group 6 (L14D-60), given leptin approximately 14 days before pregnancy, Group 7 was non-pregnant rats receiving leptin for a period of 20 days (LNP). Group 8, given 60 ug / kg /day of leptin with 600 ug / kg /day of xanthenone (XNT), an ACE2 stimulant from day -1 of pregnancy (L+ACE2a), while group 9 was given 600 ug / kg /day of XNT alone starting from day 1 of pregnancy (ACE2a). Group 10 was given 120 ug / kg /day of Leptin starting from day 1 of pregnancy (LD1-l20). SBP, serum ACE, ACE2, endothelin-l, E-selectin and ICAM-1 levels were estimated. ACE2, endothelin-l, Eselectin and ICAM-l gene expressions were determined in the kidney and aorta. Data were analysed using ANOYA and post-hoc analysis, data are presented as mean ± S.E.M. Compared to group 1, SBP was higher in the leptin only treated group (P<O.OOI) and lower in rats treated with xanthenone alone (P< 0.01). ACE2 activity and expression were lower in leptin only treated rats (P<O.05). Urine protein excretion, serum endothelin-l, serum E-selectin, and ICAM-1 levels were significantly higher than controls in leptin only treated rats (P<0.05) but not in the others. It seems, leptin administration during pregnancy significantly increases SBP, urinary protein excretion, levels and expression of markers of endothelial activation, but decreases the level and expression of ACE2. These effects are prevented by xanthenone, implicating the role of ACE2 in leptin-induced raised blood pressure and proteinuria during pregnancy. However, further studies are required to examine the underlying mechanism responsible for this and its relevance to preeclampsia in humans.

Metadata

Item Type: Thesis (PhD)
Creators:
Creators
Email / ID Num.
Ibrahim Al-Shaikhli, Hisham S
2009410054
Contributors:
Contribution
Name
Email / ID Num.
Thesis advisor
Gurcharan Singh, Harbinder Jeet Singh (Prof. Dr.)
UNSPECIFIED
Thesis advisor
Froemming, Gabriele Ruth Anisah (Assoc. Prof. Dr. )
UNSPECIFIED
Thesis advisor
Omar, Effat (Dr.)
UNSPECIFIED
Subjects: R Medicine > RG Gynecology and obstetrics > Obstetrics
Divisions: Universiti Teknologi MARA, Shah Alam > Faculty of Medicine
Programme: Doctor of Philosophy
Keywords: Proteinuria; Raised leptin levels; Blood pressure
Date: July 2014
URI: https://ir.uitm.edu.my/id/eprint/16104
Edit Item
Edit Item

Download

[thumbnail of TP_HISHAM S IBRAHIM AL-SHAIKHLI MD 14_5.pdf] Text
TP_HISHAM S IBRAHIM AL-SHAIKHLI MD 14_5.pdf

Download (1MB)

Digital Copy

Digital (fulltext) is available at:

Physical Copy

Physical status and holdings:
Item Status:

ID Number

16104

Indexing

Statistic

Statistic details