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Involvement of AT1 angiotensin receptors in the vasomodulatory effect of des-aspartate-angiotensin I in the rat renal vasculature

Angiotensin II is known to act primarily on the angiotensin AT1 receptors to mediate its physiological and pathological actions. Des-aspartate-angiotensin I (DAA-I) is a bioactive angiotensin peptide and have been shown to have contrasting vascular actions to angiotensin II. Previous work in this l...

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Main Authors: Dharmani, M., Mustafa, Mohd Rais, Achike, F.I., Sim, M.K.
Format: Article
Language:English
Published: Elsevier 2008
Subjects:
R Medicine
RM Therapeutics. Pharmacology
Online Access:http://eprints.um.edu.my/2448/1/Involvement_of_AT1_angiotensin_receptors_in_the_vasomodulatory_effect_of_des-aspartate-angiotensin_I_in_the_rat_renal_vasculature.pdf
http://eprints.um.edu.my/2448/
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spelling my.um.eprints.24482019-12-18T06:26:36Z http://eprints.um.edu.my/2448/ Involvement of AT1 angiotensin receptors in the vasomodulatory effect of des-aspartate-angiotensin I in the rat renal vasculature Dharmani, M. Mustafa, Mohd Rais Achike, F.I. Sim, M.K. R Medicine RM Therapeutics. Pharmacology Angiotensin II is known to act primarily on the angiotensin AT1 receptors to mediate its physiological and pathological actions. Des-aspartate-angiotensin I (DAA-I) is a bioactive angiotensin peptide and have been shown to have contrasting vascular actions to angiotensin II. Previous work in this laboratory has demonstrated an overwhelming vasodepressor modulation on angiotensin II-induced vasoconstriction by DAA-I. The present study investigated the involvement of the AT1 receptor in the actions of DAA-I on angiotensin IIinduced vascular actions in the renal vasculature of normotensive Wistar–Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and streptozotocin (STZ)-induced diabetic rats. The findings revealed that the angiotensin receptor in rat kidney homogenate was mainly of the AT1 subtype. The AT1 receptor density was significantly higher in the kidney of the SHR. The increase in AT1 receptor density was also confirmed by RT-PCR and Western blot analysis. In contrast, AT1 receptor density was significantly reduced in the kidney of the streptozotocininduced diabetic rat. Perfusion with 10 �9 M DAA-I reduced the AT1 receptor density in the kidneys of WKY and SHR rats suggesting that the previously observed vasodepressor modulation of the nonapeptide could be due to down-regulation or internalization of AT1 receptors. RT-PCR and Western blot analysis showed no significant changes in the content of AT1 receptor mRNA and protein. This supports the suggestion that DAA-I causes internalization of AT1 receptors. In the streptozotocin-induced diabetic rat, no significant changes in renal AT1 receptor density and expression were seen when its kidneys were similarly perfused with DAA-I. Elsevier 2008-05-28 Article PeerReviewed application/pdf en http://eprints.um.edu.my/2448/1/Involvement_of_AT1_angiotensin_receptors_in_the_vasomodulatory_effect_of_des-aspartate-angiotensin_I_in_the_rat_renal_vasculature.pdf Dharmani, M. and Mustafa, Mohd Rais and Achike, F.I. and Sim, M.K. (2008) Involvement of AT1 angiotensin receptors in the vasomodulatory effect of des-aspartate-angiotensin I in the rat renal vasculature. Peptides, 29 (10). pp. 1773-1780.
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
language English
topic R Medicine
RM Therapeutics. Pharmacology
spellingShingle R Medicine
RM Therapeutics. Pharmacology
Dharmani, M.
Mustafa, Mohd Rais
Achike, F.I.
Sim, M.K.
Involvement of AT1 angiotensin receptors in the vasomodulatory effect of des-aspartate-angiotensin I in the rat renal vasculature
description Angiotensin II is known to act primarily on the angiotensin AT1 receptors to mediate its physiological and pathological actions. Des-aspartate-angiotensin I (DAA-I) is a bioactive angiotensin peptide and have been shown to have contrasting vascular actions to angiotensin II. Previous work in this laboratory has demonstrated an overwhelming vasodepressor modulation on angiotensin II-induced vasoconstriction by DAA-I. The present study investigated the involvement of the AT1 receptor in the actions of DAA-I on angiotensin IIinduced vascular actions in the renal vasculature of normotensive Wistar–Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and streptozotocin (STZ)-induced diabetic rats. The findings revealed that the angiotensin receptor in rat kidney homogenate was mainly of the AT1 subtype. The AT1 receptor density was significantly higher in the kidney of the SHR. The increase in AT1 receptor density was also confirmed by RT-PCR and Western blot analysis. In contrast, AT1 receptor density was significantly reduced in the kidney of the streptozotocininduced diabetic rat. Perfusion with 10 �9 M DAA-I reduced the AT1 receptor density in the kidneys of WKY and SHR rats suggesting that the previously observed vasodepressor modulation of the nonapeptide could be due to down-regulation or internalization of AT1 receptors. RT-PCR and Western blot analysis showed no significant changes in the content of AT1 receptor mRNA and protein. This supports the suggestion that DAA-I causes internalization of AT1 receptors. In the streptozotocin-induced diabetic rat, no significant changes in renal AT1 receptor density and expression were seen when its kidneys were similarly perfused with DAA-I.
format Article
author Dharmani, M.
Mustafa, Mohd Rais
Achike, F.I.
Sim, M.K.
author_facet Dharmani, M.
Mustafa, Mohd Rais
Achike, F.I.
Sim, M.K.
author_sort Dharmani, M.
title Involvement of AT1 angiotensin receptors in the vasomodulatory effect of des-aspartate-angiotensin I in the rat renal vasculature
title_short Involvement of AT1 angiotensin receptors in the vasomodulatory effect of des-aspartate-angiotensin I in the rat renal vasculature
title_full Involvement of AT1 angiotensin receptors in the vasomodulatory effect of des-aspartate-angiotensin I in the rat renal vasculature
title_fullStr Involvement of AT1 angiotensin receptors in the vasomodulatory effect of des-aspartate-angiotensin I in the rat renal vasculature
title_full_unstemmed Involvement of AT1 angiotensin receptors in the vasomodulatory effect of des-aspartate-angiotensin I in the rat renal vasculature
title_sort involvement of at1 angiotensin receptors in the vasomodulatory effect of des-aspartate-angiotensin i in the rat renal vasculature
publisher Elsevier
publishDate 2008
url http://eprints.um.edu.my/2448/1/Involvement_of_AT1_angiotensin_receptors_in_the_vasomodulatory_effect_of_des-aspartate-angiotensin_I_in_the_rat_renal_vasculature.pdf
http://eprints.um.edu.my/2448/
_version_ 1654960585030238208
score 13.211869

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