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

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

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 suppress...

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Main Author: Ibrahim Al-Shaikhli, Hisham S
Format: Thesis
Language:English
Published: 2014
Subjects:
Obstetrics
Online Access:https://ir.uitm.edu.my/id/eprint/16104/1/TP_HISHAM%20S%20IBRAHIM%20AL-SHAIKHLI%20MD%2014_5.pdf
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spelling my-uitm-ir.161042022-04-01T02:38:11Z 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 2014-07 Ibrahim Al-Shaikhli, Hisham S Obstetrics 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. 2014-07 Thesis https://ir.uitm.edu.my/id/eprint/16104/ https://ir.uitm.edu.my/id/eprint/16104/1/TP_HISHAM%20S%20IBRAHIM%20AL-SHAIKHLI%20MD%2014_5.pdf text en public phd doctoral Universiti Teknologi MARA Faculty of Medicine Gurcharan Singh, Harbinder Jeet Singh (Prof. Dr.) Froemming, Gabriele Ruth Anisah (Assoc. Prof. Dr. ) Omar, Effat (Dr.)
institution Universiti Teknologi MARA
collection UiTM Institutional Repository
language English
advisor Gurcharan Singh, Harbinder Jeet Singh (Prof. Dr.)
Froemming, Gabriele Ruth Anisah (Assoc. Prof. Dr. )
Omar, Effat (Dr.)
topic Obstetrics
spellingShingle Obstetrics
Ibrahim Al-Shaikhli, Hisham S
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
description 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.
format Thesis
qualification_name Doctor of Philosophy (PhD.)
qualification_level Doctorate
author Ibrahim Al-Shaikhli, Hisham S
author_facet Ibrahim Al-Shaikhli, Hisham S
author_sort Ibrahim Al-Shaikhli, Hisham S
title 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
granting_institution Universiti Teknologi MARA
granting_department Faculty of Medicine
publishDate 2014
url https://ir.uitm.edu.my/id/eprint/16104/1/TP_HISHAM%20S%20IBRAHIM%20AL-SHAIKHLI%20MD%2014_5.pdf
_version_ 1783733483212898304

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