Sympathoexcitation by central ANG II: Roles for AT1 receptor upregulation and NAD(P)H oxidase in RVLM

Lie Gao, Wei Wang, Yulong Li, Harold D Schultz, Dongmei Liu, Kurtis G. Cornish, Irving H Zucker

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Abstract

Chronic heart failure is often associated with sympathoexcitation and blunted arterial baroreflex function. These phenomena have been causally linked to elevated central ANG II mechanisms. Recent studies have shown that NAD(P)H oxidase-derived reactive oxygen species (ROS) are important mediators of ANG II signaling and therefore might play an essential role in these interactions. The aims of this study were to determine whether central subchronic infusion of ANG II in normal animals has effects on O2 production and expression of NAD(P)H oxidase subunits as well as ANG II type 1 (AT1) receptors in the rostral ventrolateral medulla (RVLM). Twentyfour male New Zealand White rabbits were divided into four groups and separately received a subchronic intracerebroventricular infusion of saline alone, ANG II alone, ANG II with losartan, and losartan alone for 1 wk. On day 7 of intracerebroventricular infusion, mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) values were recorded, and arterial baroreflex sensitivity was evaluated while animals were in the conscious state. We found that ANG II significantly increased baseline RSNA (161.9%; P < 0.05), mRNA and protein expression of AT1 receptors (mRNA, 66.7%; P < 0.05; protein, 85.1%; P < 0.05), NAD(P)H oxidase subunits (mRNA, 120.0-200.0%; P < 0.05; protein, 90.9-197.0%; P < 0.05), and O2- production (83.2%; P < 0.05) in the RVLM. In addition, impaired baroreflex control of HR (Gainmax reduced by 48.2%; P < 0.05) and RSNA (Gainmax reduced by 53.6%; P < 0.05) by ANG II was completely abolished by losartan. Losartan significantly decreased baseline RSNA (-49.5%; P < 0.05) and increased baroreflex control of HR (Gainmax increased by 64.8%; P < 0.05) and RSNA (Gainmax increased by 67.9%; P < 0.05), but had no significant effects on mRNA and protein expression of AT1 receptor and NAD(P)H oxidase subunits and O2- production in the RVLM. These data suggest that in normal rabbits, NAD(P)H oxidase-derived ROS play an important role in the modulation of sympathetic activity and arterial baroreflex function by subchronic central treatment of exogenous ANG II via AT1 receptors.

Original languageEnglish (US)
Pages (from-to)H2271-H2279
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume288
Issue number5 57-5
DOIs
StatePublished - May 1 2005

Fingerprint

Baroreflex
NADPH Oxidase
Losartan
Up-Regulation
Kidney
Intraventricular Infusions
Messenger RNA
Heart Rate
Reactive Oxygen Species
Proteins
Rabbits
Arterial Pressure
Heart Failure

Keywords

  • Angiotensin II type 1 receptor
  • Baroreflex
  • Free radicals
  • Reactive oxygen species
  • Renal sympathetic nerve activity
  • Rostral ventrolateral medulla

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Sympathoexcitation by central ANG II : Roles for AT1 receptor upregulation and NAD(P)H oxidase in RVLM. / Gao, Lie; Wang, Wei; Li, Yulong; Schultz, Harold D; Liu, Dongmei; Cornish, Kurtis G.; Zucker, Irving H.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 288, No. 5 57-5, 01.05.2005, p. H2271-H2279.

Research output: Contribution to journalArticle

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abstract = "Chronic heart failure is often associated with sympathoexcitation and blunted arterial baroreflex function. These phenomena have been causally linked to elevated central ANG II mechanisms. Recent studies have shown that NAD(P)H oxidase-derived reactive oxygen species (ROS) are important mediators of ANG II signaling and therefore might play an essential role in these interactions. The aims of this study were to determine whether central subchronic infusion of ANG II in normal animals has effects on O2 production and expression of NAD(P)H oxidase subunits as well as ANG II type 1 (AT1) receptors in the rostral ventrolateral medulla (RVLM). Twentyfour male New Zealand White rabbits were divided into four groups and separately received a subchronic intracerebroventricular infusion of saline alone, ANG II alone, ANG II with losartan, and losartan alone for 1 wk. On day 7 of intracerebroventricular infusion, mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) values were recorded, and arterial baroreflex sensitivity was evaluated while animals were in the conscious state. We found that ANG II significantly increased baseline RSNA (161.9{\%}; P < 0.05), mRNA and protein expression of AT1 receptors (mRNA, 66.7{\%}; P < 0.05; protein, 85.1{\%}; P < 0.05), NAD(P)H oxidase subunits (mRNA, 120.0-200.0{\%}; P < 0.05; protein, 90.9-197.0{\%}; P < 0.05), and O2- production (83.2{\%}; P < 0.05) in the RVLM. In addition, impaired baroreflex control of HR (Gainmax reduced by 48.2{\%}; P < 0.05) and RSNA (Gainmax reduced by 53.6{\%}; P < 0.05) by ANG II was completely abolished by losartan. Losartan significantly decreased baseline RSNA (-49.5{\%}; P < 0.05) and increased baroreflex control of HR (Gainmax increased by 64.8{\%}; P < 0.05) and RSNA (Gainmax increased by 67.9{\%}; P < 0.05), but had no significant effects on mRNA and protein expression of AT1 receptor and NAD(P)H oxidase subunits and O2- production in the RVLM. These data suggest that in normal rabbits, NAD(P)H oxidase-derived ROS play an important role in the modulation of sympathetic activity and arterial baroreflex function by subchronic central treatment of exogenous ANG II via AT1 receptors.",
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AU - Zucker, Irving H

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