NADPH oxidase-derived superoxide anion mediates angiotensin II-enhanced carotid body chemoreceptor sensitivity in heart failure rabbits.

Abstract:

OBJECTIVE:A previous study from this laboratory showed that elevation of endogenous angiotensin II (Ang II) and upregulation of the angiotensin II type 1 (AT(1)) receptor in the carotid body (CB) are involved in the enhanced peripheral chemoreceptor sensitivity in rabbits with chronic heart failure (CHF). NADPH oxidase-derived superoxide anion mediates the effects of Ang II in many organs. We investigated whether this signaling pathway may mediate the enhanced peripheral chemoreceptor sensitivity induced by Ang II in CHF rabbits. METHODS AND RESULTS:By recording single-unit activity from the carotid sinus nerve in isolated preparations, we found that phenylarsine oxide 2 muM (PAO, NADPH oxidase inhibitor) and TEMPOL 1 mM (superoxide dismutase mimetic) significantly decreased not only the Ang II-enhanced CB chemoreceptor responses to different levels of hypoxia in sham rabbits (Delta-12.5+/-0.8 and Delta-12.8+/-0.9 imp/s at 40.7+/-2.3 mm Hg of PO(2), and Delta-5.6+/-0.5 and Delta-5.3+/-0.4 imp/s at 60.2+/-3.1 mm Hg of PO(2), p<0.05, respectively) but also the CHF-induced elevation of CB chemoreceptor responses to different levels of hypoxia (Delta-13.6+/-1.1 and Delta-13.7+/-0.9 imp/s at 40.9+/-3.1 mm Hg of PO(2), and Delta-6.7+/-1.2 and Delta-6.6+/-0.8 imp/s at 59.8+/-3.5 mm Hg of PO(2), p<0.05). In addition, mRNA and protein expressions of NADPH oxidase components (gp91(phox), p40(phox) and p47(phox)) were higher in the CB from CHF rabbits compared to sham rabbits. Furthermore, 100 pM Ang II induced an increase in superoxide production in CB homogenates from sham rabbits, which was similar to that in CB homogenate from CHF rabbits. PAO and Tempol inhibited the Ang II- and CHF-enhanced superoxide anion production. CONCLUSIONS:These results suggest that the enhanced peripheral chemoreceptor sensitivity mediated by Ang II in CHF rabbits occurs via a NADPH oxidase-superoxide signaling pathway.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Li YL,Gao L,Zucker IH,Schultz HD

doi

10.1016/j.cardiores.2007.04.006

subject

Has Abstract

pub_date

2007-08-01 00:00:00

pages

546-54

issue

3

eissn

0008-6363

issn

1755-3245

pii

S0008-6363(07)00161-7

journal_volume

75

pub_type

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