Imbalance of angiotensin type 1 receptor and angiotensin II type 2 receptor in the rostral ventrolateral medulla potential mechanism for sympathetic overactivity in heart failure

Lie Gao, Wei Zhong Wang, Wei Wang, Irving H Zucker

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86 Citations (Scopus)

Abstract

Upregulation of angiotensin II type 1 receptors (AT1R) in the rostral ventrolateral medulla (RVLM) contributes to the sympathoexcitation in the chronic heart failure (CHF). However, the role of angiotensin II type 2 receptor (AT2R) is not clear. In this study, we measured AT 1R and AT2R protein expression in the RVLM and determined their effects on renal sympathetic nerve activity, blood pressure, and heart rate in anesthetized sham and CHF rats. We found that (1) although AT 1R expression in the RVLM was upregulated, the AT2R was significantly downregulated (CHF: 0.06±0.02 versus sham: 0.15±0.02, p<0.05); (2) simultaneously stimulating RVLM AT 1R and AT2R by angiotensin II evoked sympathoexcitation, hypertension, and tachycardia in both sham and CHF rats with greater responses in CHF; (3) stimulating RVLM AT1R with angiotensin II plus the specific AT 2R antagonist PD123319 induced a larger sympathoexcitatory response man simultaneously stimulating AT1R and AT2R in sham rats, but not in CHF; (4) activating RVLM AT2R with CGP42112 induced a sympathoinhibition, hypotension, and bradycardia only in sham rats (renal sympathetic nerve activity: 36.4±S.1% of baseline versus 102±3.9% of baseline in artificial cerebrospinal fluid, P<0.05); (5) pretreatment with 5,8,11,14-eicosatetraynoic acid, a general inhibitor of arachidonic acid metabolism, into the RVLM attenuates the CGP42112-induced sympathoinhibition. These results suggest that AT2R in the RVLM exhibits an inhibitory effect on sympathetic outflow, which is, at least partially, mediated by an arachidonic acid metabolic pathway. These data implicate a downregulation in the AT2R as a contributory factor in the sympathoexcitation in CHF.

Original languageEnglish (US)
Pages (from-to)708-714
Number of pages7
JournalHypertension
Volume52
Issue number4
DOIs
StatePublished - Oct 1 2008

Fingerprint

Angiotensin Type 2 Receptor
Angiotensin Type 1 Receptor
Heart Failure
Arachidonic Acid
Angiotensin II
Down-Regulation
5,8,11,14-Eicosatetraynoic Acid
Kidney
Bradycardia
Metabolic Networks and Pathways
Tachycardia
Hypotension
Cerebrospinal Fluid
Up-Regulation
Heart Rate
Blood Pressure
Hypertension

Keywords

  • Angiotensin II type 1 receptor
  • Angiotensin II type 2 receptor
  • Rostral ventrolateral medulla
  • Sympathetic outflow

ASJC Scopus subject areas

  • Internal Medicine

Cite this

@article{e5a5d8db45814b1985e7d7f9a2af3b08,
title = "Imbalance of angiotensin type 1 receptor and angiotensin II type 2 receptor in the rostral ventrolateral medulla potential mechanism for sympathetic overactivity in heart failure",
abstract = "Upregulation of angiotensin II type 1 receptors (AT1R) in the rostral ventrolateral medulla (RVLM) contributes to the sympathoexcitation in the chronic heart failure (CHF). However, the role of angiotensin II type 2 receptor (AT2R) is not clear. In this study, we measured AT 1R and AT2R protein expression in the RVLM and determined their effects on renal sympathetic nerve activity, blood pressure, and heart rate in anesthetized sham and CHF rats. We found that (1) although AT 1R expression in the RVLM was upregulated, the AT2R was significantly downregulated (CHF: 0.06±0.02 versus sham: 0.15±0.02, p<0.05); (2) simultaneously stimulating RVLM AT 1R and AT2R by angiotensin II evoked sympathoexcitation, hypertension, and tachycardia in both sham and CHF rats with greater responses in CHF; (3) stimulating RVLM AT1R with angiotensin II plus the specific AT 2R antagonist PD123319 induced a larger sympathoexcitatory response man simultaneously stimulating AT1R and AT2R in sham rats, but not in CHF; (4) activating RVLM AT2R with CGP42112 induced a sympathoinhibition, hypotension, and bradycardia only in sham rats (renal sympathetic nerve activity: 36.4±S.1{\%} of baseline versus 102±3.9{\%} of baseline in artificial cerebrospinal fluid, P<0.05); (5) pretreatment with 5,8,11,14-eicosatetraynoic acid, a general inhibitor of arachidonic acid metabolism, into the RVLM attenuates the CGP42112-induced sympathoinhibition. These results suggest that AT2R in the RVLM exhibits an inhibitory effect on sympathetic outflow, which is, at least partially, mediated by an arachidonic acid metabolic pathway. These data implicate a downregulation in the AT2R as a contributory factor in the sympathoexcitation in CHF.",
keywords = "Angiotensin II type 1 receptor, Angiotensin II type 2 receptor, Rostral ventrolateral medulla, Sympathetic outflow",
author = "Lie Gao and Wang, {Wei Zhong} and Wei Wang and Zucker, {Irving H}",
year = "2008",
month = "10",
day = "1",
doi = "10.1161/HYPERTENSIONAHA.108.116228",
language = "English (US)",
volume = "52",
pages = "708--714",
journal = "Hypertension",
issn = "0194-911X",
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TY - JOUR

T1 - Imbalance of angiotensin type 1 receptor and angiotensin II type 2 receptor in the rostral ventrolateral medulla potential mechanism for sympathetic overactivity in heart failure

AU - Gao, Lie

AU - Wang, Wei Zhong

AU - Wang, Wei

AU - Zucker, Irving H

PY - 2008/10/1

Y1 - 2008/10/1

N2 - Upregulation of angiotensin II type 1 receptors (AT1R) in the rostral ventrolateral medulla (RVLM) contributes to the sympathoexcitation in the chronic heart failure (CHF). However, the role of angiotensin II type 2 receptor (AT2R) is not clear. In this study, we measured AT 1R and AT2R protein expression in the RVLM and determined their effects on renal sympathetic nerve activity, blood pressure, and heart rate in anesthetized sham and CHF rats. We found that (1) although AT 1R expression in the RVLM was upregulated, the AT2R was significantly downregulated (CHF: 0.06±0.02 versus sham: 0.15±0.02, p<0.05); (2) simultaneously stimulating RVLM AT 1R and AT2R by angiotensin II evoked sympathoexcitation, hypertension, and tachycardia in both sham and CHF rats with greater responses in CHF; (3) stimulating RVLM AT1R with angiotensin II plus the specific AT 2R antagonist PD123319 induced a larger sympathoexcitatory response man simultaneously stimulating AT1R and AT2R in sham rats, but not in CHF; (4) activating RVLM AT2R with CGP42112 induced a sympathoinhibition, hypotension, and bradycardia only in sham rats (renal sympathetic nerve activity: 36.4±S.1% of baseline versus 102±3.9% of baseline in artificial cerebrospinal fluid, P<0.05); (5) pretreatment with 5,8,11,14-eicosatetraynoic acid, a general inhibitor of arachidonic acid metabolism, into the RVLM attenuates the CGP42112-induced sympathoinhibition. These results suggest that AT2R in the RVLM exhibits an inhibitory effect on sympathetic outflow, which is, at least partially, mediated by an arachidonic acid metabolic pathway. These data implicate a downregulation in the AT2R as a contributory factor in the sympathoexcitation in CHF.

AB - Upregulation of angiotensin II type 1 receptors (AT1R) in the rostral ventrolateral medulla (RVLM) contributes to the sympathoexcitation in the chronic heart failure (CHF). However, the role of angiotensin II type 2 receptor (AT2R) is not clear. In this study, we measured AT 1R and AT2R protein expression in the RVLM and determined their effects on renal sympathetic nerve activity, blood pressure, and heart rate in anesthetized sham and CHF rats. We found that (1) although AT 1R expression in the RVLM was upregulated, the AT2R was significantly downregulated (CHF: 0.06±0.02 versus sham: 0.15±0.02, p<0.05); (2) simultaneously stimulating RVLM AT 1R and AT2R by angiotensin II evoked sympathoexcitation, hypertension, and tachycardia in both sham and CHF rats with greater responses in CHF; (3) stimulating RVLM AT1R with angiotensin II plus the specific AT 2R antagonist PD123319 induced a larger sympathoexcitatory response man simultaneously stimulating AT1R and AT2R in sham rats, but not in CHF; (4) activating RVLM AT2R with CGP42112 induced a sympathoinhibition, hypotension, and bradycardia only in sham rats (renal sympathetic nerve activity: 36.4±S.1% of baseline versus 102±3.9% of baseline in artificial cerebrospinal fluid, P<0.05); (5) pretreatment with 5,8,11,14-eicosatetraynoic acid, a general inhibitor of arachidonic acid metabolism, into the RVLM attenuates the CGP42112-induced sympathoinhibition. These results suggest that AT2R in the RVLM exhibits an inhibitory effect on sympathetic outflow, which is, at least partially, mediated by an arachidonic acid metabolic pathway. These data implicate a downregulation in the AT2R as a contributory factor in the sympathoexcitation in CHF.

KW - Angiotensin II type 1 receptor

KW - Angiotensin II type 2 receptor

KW - Rostral ventrolateral medulla

KW - Sympathetic outflow

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