Angiotensin II enhances carotid body chemoreflex control of sympathetic outflow in chronic heart failure rabbits

Yulong Li, Xiao Hong Xia, Hong Zheng, Lie Gao, Yi Fan Li, Dongmei Liu, Kaushik P Patel, Wei Wang, Harold D Schultz

Research output: Contribution to journalArticle

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Abstract

Objectives: We investigated whether Angiotensin II (Ang II) modulates peripheral chemoreflex function through carotid body (CB) chemoreceptors in chronic heart failure (CHF). Methods: We measured renal sympathetic nerve activity (RSNA) in response to graded hypoxia before and after intravenous administration of Ang II (20 ng/kg/min, i.v. 30 min) or AT1 receptor antagonist (L-158,809, 0.33 mg/kg, i.v.) in conscious sham and pacing-induced CHF rabbits. We also investigated the effects of Ang II (100 pM) and L-158,809 (1 μM) on CB chemoreceptor activity in vascularly isolated-perfused CB preparations from sham and CHF rabbits. Results: Ang II enhanced hypoxia-induced RSNA increases in sham rabbits but not in CHF rabbits. Conversely, L-158,809 attenuated hypoxia-induced responses in RSNA in CHF rabbits but not in sham rabbits. Using RT-PCR, Western blotting, and immunocytochemistry, we found that the mRNA and protein expression of AT1 receptor in the CB from CHF rabbits were greater than that in sham rabbits. CB chemoreceptor afferent activity during normoxia and graded hypoxia was increased in CHF rabbits compared with sham rabbits. Ang II increased the response of CB chemoreceptors to hypoxia in sham rabbits but not CHF rabbits. L-158,809 decreased CB chemoreceptor responses to hypoxia in CHF rabbits but not in sham rabbits. Conclusions: These results indicate that elevation of Ang II and concomitant upregulation of AT1 receptor in the CB contribute to the increased CB chemoreceptor activity and enhanced peripheral chemoreflex function in CHF.

Original languageEnglish (US)
Pages (from-to)129-138
Number of pages10
JournalCardiovascular research
Volume71
Issue number1
DOIs
StatePublished - Jul 1 2006

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Carotid Body
Angiotensin II
Heart Failure
Rabbits
Kidney
Intravenous Administration

Keywords

  • Angiotensin
  • Autonomic nervous system
  • Chemoreflex
  • Heart failure
  • Hypoxia

ASJC Scopus subject areas

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

Cite this

Angiotensin II enhances carotid body chemoreflex control of sympathetic outflow in chronic heart failure rabbits. / Li, Yulong; Xia, Xiao Hong; Zheng, Hong; Gao, Lie; Li, Yi Fan; Liu, Dongmei; Patel, Kaushik P; Wang, Wei; Schultz, Harold D.

In: Cardiovascular research, Vol. 71, No. 1, 01.07.2006, p. 129-138.

Research output: Contribution to journalArticle

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abstract = "Objectives: We investigated whether Angiotensin II (Ang II) modulates peripheral chemoreflex function through carotid body (CB) chemoreceptors in chronic heart failure (CHF). Methods: We measured renal sympathetic nerve activity (RSNA) in response to graded hypoxia before and after intravenous administration of Ang II (20 ng/kg/min, i.v. 30 min) or AT1 receptor antagonist (L-158,809, 0.33 mg/kg, i.v.) in conscious sham and pacing-induced CHF rabbits. We also investigated the effects of Ang II (100 pM) and L-158,809 (1 μM) on CB chemoreceptor activity in vascularly isolated-perfused CB preparations from sham and CHF rabbits. Results: Ang II enhanced hypoxia-induced RSNA increases in sham rabbits but not in CHF rabbits. Conversely, L-158,809 attenuated hypoxia-induced responses in RSNA in CHF rabbits but not in sham rabbits. Using RT-PCR, Western blotting, and immunocytochemistry, we found that the mRNA and protein expression of AT1 receptor in the CB from CHF rabbits were greater than that in sham rabbits. CB chemoreceptor afferent activity during normoxia and graded hypoxia was increased in CHF rabbits compared with sham rabbits. Ang II increased the response of CB chemoreceptors to hypoxia in sham rabbits but not CHF rabbits. L-158,809 decreased CB chemoreceptor responses to hypoxia in CHF rabbits but not in sham rabbits. Conclusions: These results indicate that elevation of Ang II and concomitant upregulation of AT1 receptor in the CB contribute to the increased CB chemoreceptor activity and enhanced peripheral chemoreflex function in CHF.",
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AB - Objectives: We investigated whether Angiotensin II (Ang II) modulates peripheral chemoreflex function through carotid body (CB) chemoreceptors in chronic heart failure (CHF). Methods: We measured renal sympathetic nerve activity (RSNA) in response to graded hypoxia before and after intravenous administration of Ang II (20 ng/kg/min, i.v. 30 min) or AT1 receptor antagonist (L-158,809, 0.33 mg/kg, i.v.) in conscious sham and pacing-induced CHF rabbits. We also investigated the effects of Ang II (100 pM) and L-158,809 (1 μM) on CB chemoreceptor activity in vascularly isolated-perfused CB preparations from sham and CHF rabbits. Results: Ang II enhanced hypoxia-induced RSNA increases in sham rabbits but not in CHF rabbits. Conversely, L-158,809 attenuated hypoxia-induced responses in RSNA in CHF rabbits but not in sham rabbits. Using RT-PCR, Western blotting, and immunocytochemistry, we found that the mRNA and protein expression of AT1 receptor in the CB from CHF rabbits were greater than that in sham rabbits. CB chemoreceptor afferent activity during normoxia and graded hypoxia was increased in CHF rabbits compared with sham rabbits. Ang II increased the response of CB chemoreceptors to hypoxia in sham rabbits but not CHF rabbits. L-158,809 decreased CB chemoreceptor responses to hypoxia in CHF rabbits but not in sham rabbits. Conclusions: These results indicate that elevation of Ang II and concomitant upregulation of AT1 receptor in the CB contribute to the increased CB chemoreceptor activity and enhanced peripheral chemoreflex function in CHF.

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