Copyright © 2006, European Society of Cardiology
Angiotensin II enhances carotid body chemoreflex control of sympathetic outflow in chronic heart failure rabbits
aDepartment of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5850, USA
bDepartment of Pathophysiology, Hebei Academy of Medical Science, Shijiazhuang, Hebei 050021, People's Republic of China
cDivision of Basic Biomedical Sciences, University of South Dakota School of Medicine, Vermillion, SD 57069-2390, USA
* Corresponding author. Tel.: +1 402 559 7167; fax: +1 402 559 4438. Email address: hschultz{at}unmc.edu
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 (20ng/kg/min, i.v. 30min) or AT1 receptor antagonist (L-158,809, 0.33mg/kg, i.v.) in conscious sham and pacing-induced CHF rabbits. We also investigated the effects of Ang II (100pM) and L-158,809 (1µM) 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.
KEYWORDS Angiotensin; Autonomic nervous system; Chemoreflex; Heart failure; Hypoxia
Time for primary review 26 days
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