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

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 microM) 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.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Li YL,Xia XH,Zheng H,Gao L,Li YF,Liu D,Patel KP,Wang W,Schultz HD

doi

10.1016/j.cardiores.2006.03.017

subject

Has Abstract

pub_date

2006-07-01 00:00:00

pages

129-38

issue

1

eissn

0008-6363

issn

1755-3245

pii

S0008-6363(06)00144-1

journal_volume

71

pub_type

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