Reduced sensitivity of the renal vasculature to angiotensin II in young rats: the role of the angiotensin type 2 receptor

Russell D Brown, Lucinda M Hilliard, Katrina M Mirabito, Laura C Firth, Karen M Moritz, Roger G Evans, Katherine M Denton

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

Background:The angiotensin type-2 receptor (AT2R) opposes the vasoconstrictor actions of angiotensin II (AngII) mediated through the angiotensin type-1 receptor (AT1R). Renal AT2R levels are high during fetal life, but decrease significantly during postnatal maturation. To provide insight into the functional role of the AT2R in the kidney during postnatal development, we investigated the effects of AT2R antagonism on cardiovascular responses to AngII in young and adult male rats.Methods:In anesthetized 3- and 6-wk-old male Sprague-Dawley rats, mean arterial pressure (MAP) and renal blood flow (RBF) were measured in response to AngII in the presence of vehicle treatment or AT2R blockade with PD123319.Results:The pressor effect of AngII and associated reduction in RBF were significantly less in 3-wk- than 6-wk-old rats. AT2R blockade potentiated the reduction in RBF in response to AngII in 3-wk-old rats only.Conclusion:In young rats, the AT2R modulates the response to AngII, blunting renal vasoconstriction. This effect is attenuated with age in association with a developmental reduction in renal AT2R expression. These findings may have implications for the development of novel therapies that target the renin-angiotensin system for the improvement of renal function in term and, in particular, preterm infants.Pediatric Research (2014); doi:10.1038/pr.2014.121.
Original languageEnglish
Pages (from-to)448 - 452
Number of pages5
JournalPediatric Research
Volume76
Issue number5
DOIs
Publication statusPublished - 2014

Cite this

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title = "Reduced sensitivity of the renal vasculature to angiotensin II in young rats: the role of the angiotensin type 2 receptor",
abstract = "Background:The angiotensin type-2 receptor (AT2R) opposes the vasoconstrictor actions of angiotensin II (AngII) mediated through the angiotensin type-1 receptor (AT1R). Renal AT2R levels are high during fetal life, but decrease significantly during postnatal maturation. To provide insight into the functional role of the AT2R in the kidney during postnatal development, we investigated the effects of AT2R antagonism on cardiovascular responses to AngII in young and adult male rats.Methods:In anesthetized 3- and 6-wk-old male Sprague-Dawley rats, mean arterial pressure (MAP) and renal blood flow (RBF) were measured in response to AngII in the presence of vehicle treatment or AT2R blockade with PD123319.Results:The pressor effect of AngII and associated reduction in RBF were significantly less in 3-wk- than 6-wk-old rats. AT2R blockade potentiated the reduction in RBF in response to AngII in 3-wk-old rats only.Conclusion:In young rats, the AT2R modulates the response to AngII, blunting renal vasoconstriction. This effect is attenuated with age in association with a developmental reduction in renal AT2R expression. These findings may have implications for the development of novel therapies that target the renin-angiotensin system for the improvement of renal function in term and, in particular, preterm infants.Pediatric Research (2014); doi:10.1038/pr.2014.121.",
author = "Brown, {Russell D} and Hilliard, {Lucinda M} and Mirabito, {Katrina M} and Firth, {Laura C} and Moritz, {Karen M} and Evans, {Roger G} and Denton, {Katherine M}",
year = "2014",
doi = "10.1038/pr.2014.121",
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pages = "448 -- 452",
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Reduced sensitivity of the renal vasculature to angiotensin II in young rats: the role of the angiotensin type 2 receptor. / Brown, Russell D; Hilliard, Lucinda M; Mirabito, Katrina M; Firth, Laura C; Moritz, Karen M; Evans, Roger G; Denton, Katherine M.

In: Pediatric Research, Vol. 76, No. 5, 2014, p. 448 - 452.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Reduced sensitivity of the renal vasculature to angiotensin II in young rats: the role of the angiotensin type 2 receptor

AU - Brown, Russell D

AU - Hilliard, Lucinda M

AU - Mirabito, Katrina M

AU - Firth, Laura C

AU - Moritz, Karen M

AU - Evans, Roger G

AU - Denton, Katherine M

PY - 2014

Y1 - 2014

N2 - Background:The angiotensin type-2 receptor (AT2R) opposes the vasoconstrictor actions of angiotensin II (AngII) mediated through the angiotensin type-1 receptor (AT1R). Renal AT2R levels are high during fetal life, but decrease significantly during postnatal maturation. To provide insight into the functional role of the AT2R in the kidney during postnatal development, we investigated the effects of AT2R antagonism on cardiovascular responses to AngII in young and adult male rats.Methods:In anesthetized 3- and 6-wk-old male Sprague-Dawley rats, mean arterial pressure (MAP) and renal blood flow (RBF) were measured in response to AngII in the presence of vehicle treatment or AT2R blockade with PD123319.Results:The pressor effect of AngII and associated reduction in RBF were significantly less in 3-wk- than 6-wk-old rats. AT2R blockade potentiated the reduction in RBF in response to AngII in 3-wk-old rats only.Conclusion:In young rats, the AT2R modulates the response to AngII, blunting renal vasoconstriction. This effect is attenuated with age in association with a developmental reduction in renal AT2R expression. These findings may have implications for the development of novel therapies that target the renin-angiotensin system for the improvement of renal function in term and, in particular, preterm infants.Pediatric Research (2014); doi:10.1038/pr.2014.121.

AB - Background:The angiotensin type-2 receptor (AT2R) opposes the vasoconstrictor actions of angiotensin II (AngII) mediated through the angiotensin type-1 receptor (AT1R). Renal AT2R levels are high during fetal life, but decrease significantly during postnatal maturation. To provide insight into the functional role of the AT2R in the kidney during postnatal development, we investigated the effects of AT2R antagonism on cardiovascular responses to AngII in young and adult male rats.Methods:In anesthetized 3- and 6-wk-old male Sprague-Dawley rats, mean arterial pressure (MAP) and renal blood flow (RBF) were measured in response to AngII in the presence of vehicle treatment or AT2R blockade with PD123319.Results:The pressor effect of AngII and associated reduction in RBF were significantly less in 3-wk- than 6-wk-old rats. AT2R blockade potentiated the reduction in RBF in response to AngII in 3-wk-old rats only.Conclusion:In young rats, the AT2R modulates the response to AngII, blunting renal vasoconstriction. This effect is attenuated with age in association with a developmental reduction in renal AT2R expression. These findings may have implications for the development of novel therapies that target the renin-angiotensin system for the improvement of renal function in term and, in particular, preterm infants.Pediatric Research (2014); doi:10.1038/pr.2014.121.

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