Pressor response to angiotensin II is enhanced in aged mice and associated with inflammation, vasoconstriction and oxidative stress

Quynh Nhu Dinh, Grant R. Drummond, Barbara K. Kemp-Harper, Henry Diep, T. Michael De Silva, Hyun Ah Kim, Antony Vinh, Avril A B Robertson, Matthew A Cooper, Ashley Mansell, Sophocles Chrissobolis, Christopher G. Sobey

Research output: Contribution to journalArticleResearchpeer-review

13 Citations (Scopus)

Abstract

Aging is commonly associated with chronic low-grade inflammation and hypertension but it is unknown whether a cause-effect relationship exists between them. We compared the sensitivity of young adult (8-12 w) and aged (23-31 mo) male C57Bl6J mice to develop hypertension in response to a slow-pressor dose of angiotensin II (Ang II; 0.28 mg/kg/d; 28 d). In young mice, the pressor response to Ang II was gradual and increased to 142±8 mmHg over 28 d. However, in aged mice, Ang II promptly increased SBP and reached 155±12 mmHg by 28 d. Aging increased renal but not brain expression of Ang II receptors (At1ar and At2r) and elevated AT1R:AT2R expression ratio in mesenteric artery. Maximal contractile responses of mesenteric arteries to Ang II were enhanced in aged mice and were not affected by L-NAME, indomethacin or tempol. Mesenteric arteries and thoracic aortae from aged mice exhibited higher Nox2-dependent superoxide production. Despite having higher renal expression of Nlrp3, Casp-1 and Il-1β, Ang II-induced hypertension (SBP: 139±7 mmHg) was unaffected by co-infusion of the NLRP3 inflammasome inhibitor, MCC950 (10 mg/kg/d; SBP: 145±10 mmHg). Thus, increased vascular AT1R:AT2R expression, rather than NLRP3 inflammasome activation, may contribute to enhanced responses to Ang II in aging.

Original languageEnglish
Pages (from-to)1595-1605
Number of pages11
JournalAging
Volume9
Issue number6
DOIs
Publication statusPublished - 28 Jun 2017

Keywords

  • Aging
  • Angiotensin II
  • Hypertension
  • Inflammation
  • Oxidative stress
  • Vasoconstriction

Cite this

@article{4636abe2704c49db9339bac371933515,
title = "Pressor response to angiotensin II is enhanced in aged mice and associated with inflammation, vasoconstriction and oxidative stress",
abstract = "Aging is commonly associated with chronic low-grade inflammation and hypertension but it is unknown whether a cause-effect relationship exists between them. We compared the sensitivity of young adult (8-12 w) and aged (23-31 mo) male C57Bl6J mice to develop hypertension in response to a slow-pressor dose of angiotensin II (Ang II; 0.28 mg/kg/d; 28 d). In young mice, the pressor response to Ang II was gradual and increased to 142±8 mmHg over 28 d. However, in aged mice, Ang II promptly increased SBP and reached 155±12 mmHg by 28 d. Aging increased renal but not brain expression of Ang II receptors (At1ar and At2r) and elevated AT1R:AT2R expression ratio in mesenteric artery. Maximal contractile responses of mesenteric arteries to Ang II were enhanced in aged mice and were not affected by L-NAME, indomethacin or tempol. Mesenteric arteries and thoracic aortae from aged mice exhibited higher Nox2-dependent superoxide production. Despite having higher renal expression of Nlrp3, Casp-1 and Il-1β, Ang II-induced hypertension (SBP: 139±7 mmHg) was unaffected by co-infusion of the NLRP3 inflammasome inhibitor, MCC950 (10 mg/kg/d; SBP: 145±10 mmHg). Thus, increased vascular AT1R:AT2R expression, rather than NLRP3 inflammasome activation, may contribute to enhanced responses to Ang II in aging.",
keywords = "Aging, Angiotensin II, Hypertension, Inflammation, Oxidative stress, Vasoconstriction",
author = "Dinh, {Quynh Nhu} and Drummond, {Grant R.} and Kemp-Harper, {Barbara K.} and Henry Diep and {De Silva}, {T. Michael} and Kim, {Hyun Ah} and Antony Vinh and Robertson, {Avril A B} and Cooper, {Matthew A} and Ashley Mansell and Sophocles Chrissobolis and Sobey, {Christopher G.}",
year = "2017",
month = "6",
day = "28",
doi = "10.18632/aging.101255",
language = "English",
volume = "9",
pages = "1595--1605",
journal = "Aging",
issn = "1945-4589",
publisher = "Impact Journals",
number = "6",

}

Pressor response to angiotensin II is enhanced in aged mice and associated with inflammation, vasoconstriction and oxidative stress. / Dinh, Quynh Nhu; Drummond, Grant R.; Kemp-Harper, Barbara K.; Diep, Henry; De Silva, T. Michael; Kim, Hyun Ah; Vinh, Antony; Robertson, Avril A B; Cooper, Matthew A; Mansell, Ashley; Chrissobolis, Sophocles; Sobey, Christopher G.

In: Aging, Vol. 9, No. 6, 28.06.2017, p. 1595-1605.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Pressor response to angiotensin II is enhanced in aged mice and associated with inflammation, vasoconstriction and oxidative stress

AU - Dinh, Quynh Nhu

AU - Drummond, Grant R.

AU - Kemp-Harper, Barbara K.

AU - Diep, Henry

AU - De Silva, T. Michael

AU - Kim, Hyun Ah

AU - Vinh, Antony

AU - Robertson, Avril A B

AU - Cooper, Matthew A

AU - Mansell, Ashley

AU - Chrissobolis, Sophocles

AU - Sobey, Christopher G.

PY - 2017/6/28

Y1 - 2017/6/28

N2 - Aging is commonly associated with chronic low-grade inflammation and hypertension but it is unknown whether a cause-effect relationship exists between them. We compared the sensitivity of young adult (8-12 w) and aged (23-31 mo) male C57Bl6J mice to develop hypertension in response to a slow-pressor dose of angiotensin II (Ang II; 0.28 mg/kg/d; 28 d). In young mice, the pressor response to Ang II was gradual and increased to 142±8 mmHg over 28 d. However, in aged mice, Ang II promptly increased SBP and reached 155±12 mmHg by 28 d. Aging increased renal but not brain expression of Ang II receptors (At1ar and At2r) and elevated AT1R:AT2R expression ratio in mesenteric artery. Maximal contractile responses of mesenteric arteries to Ang II were enhanced in aged mice and were not affected by L-NAME, indomethacin or tempol. Mesenteric arteries and thoracic aortae from aged mice exhibited higher Nox2-dependent superoxide production. Despite having higher renal expression of Nlrp3, Casp-1 and Il-1β, Ang II-induced hypertension (SBP: 139±7 mmHg) was unaffected by co-infusion of the NLRP3 inflammasome inhibitor, MCC950 (10 mg/kg/d; SBP: 145±10 mmHg). Thus, increased vascular AT1R:AT2R expression, rather than NLRP3 inflammasome activation, may contribute to enhanced responses to Ang II in aging.

AB - Aging is commonly associated with chronic low-grade inflammation and hypertension but it is unknown whether a cause-effect relationship exists between them. We compared the sensitivity of young adult (8-12 w) and aged (23-31 mo) male C57Bl6J mice to develop hypertension in response to a slow-pressor dose of angiotensin II (Ang II; 0.28 mg/kg/d; 28 d). In young mice, the pressor response to Ang II was gradual and increased to 142±8 mmHg over 28 d. However, in aged mice, Ang II promptly increased SBP and reached 155±12 mmHg by 28 d. Aging increased renal but not brain expression of Ang II receptors (At1ar and At2r) and elevated AT1R:AT2R expression ratio in mesenteric artery. Maximal contractile responses of mesenteric arteries to Ang II were enhanced in aged mice and were not affected by L-NAME, indomethacin or tempol. Mesenteric arteries and thoracic aortae from aged mice exhibited higher Nox2-dependent superoxide production. Despite having higher renal expression of Nlrp3, Casp-1 and Il-1β, Ang II-induced hypertension (SBP: 139±7 mmHg) was unaffected by co-infusion of the NLRP3 inflammasome inhibitor, MCC950 (10 mg/kg/d; SBP: 145±10 mmHg). Thus, increased vascular AT1R:AT2R expression, rather than NLRP3 inflammasome activation, may contribute to enhanced responses to Ang II in aging.

KW - Aging

KW - Angiotensin II

KW - Hypertension

KW - Inflammation

KW - Oxidative stress

KW - Vasoconstriction

UR - http://www.scopus.com/inward/record.url?scp=85021761128&partnerID=8YFLogxK

U2 - 10.18632/aging.101255

DO - 10.18632/aging.101255

M3 - Article

VL - 9

SP - 1595

EP - 1605

JO - Aging

JF - Aging

SN - 1945-4589

IS - 6

ER -