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

Research output: Contribution to journalArticle

91 Scopus citations

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 2008

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine

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