Regulation of central angiotensin type 1 receptors and sympathetic outflow in heart failure

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84 Scopus citations


Angiotensin type 1 receptors (AT1Rs) play a critical role in a variety of physiological functions and pathophysiological states. They have been strongly implicated in the modulation of sympathetic outflow in the brain. An understanding of the mechanisms by which AT1Rs are regulated in a variety of disease states that are characterized by sympathoexcitation is pivotal in development of new strategies for the treatment of these disorders. This review concentrates on several aspects of AT1R regulation in the setting of chronic heart failure (CHF). There is now good evidence that AT 1R expression in neurons is mediated by activation of the transcription factor activator protein 1 (AP-1). This transcription factor and its component proteins are upregulated in the rostral ventrolateral medulla of animals with CHF. Because the increase in AT1R expression and transcription factor activation can be blocked by the AT1R antagonist losartan, a positive feedback mechanism of AT1R expression in CHF is suggested. Oxidative stress has also been implicated in the regulation of receptor expression. Recent data suggest that the newly discovered catabolic enzyme angiotensin-converting enzyme 2 (ACE2) may play a role in the modulation of AT1R expression by altering the balance between the octapeptide ANG II and ANG-(1-7). Finally, exercise training reduces both central oxidative stress and AT1R expression in animals with CHF. These data strongly suggest that multiple central and peripheral influences dynamically alter AT1R expression in CHF.

Original languageEnglish (US)
Pages (from-to)H1557-H1566
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number5
StatePublished - Nov 2009


  • Neuronal signaling
  • Oxidative stress
  • Sympathetic nerve activity

ASJC Scopus subject areas

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


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