TY - JOUR
T1 - NADPH oxidase-derived superoxide anion mediates angiotensin II-enhanced carotid body chemoreceptor sensitivity in heart failure rabbits
AU - Li, Yu Long
AU - Gao, Lie
AU - Zucker, Irving H.
AU - Schultz, Harold D.
N1 - Funding Information:
The authors wish to thank Lisa Rasmussen, Kaye Talbitzer for their technical assistance, and Dr. Kurtis Cornish for his surgical assistance. This study was supported by a Program Project Grant from the Heart, Lung and Blood Institute of NIH (PO1-HL62222).
PY - 2007/8/1
Y1 - 2007/8/1
N2 - Objective: A previous study from this laboratory showed that elevation of endogenous angiotensin II (Ang II) and upregulation of the angiotensin II type 1 (AT1) 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 μM (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 (Δ-12.5 ± 0.8 and Δ-12.8 ± 0.9 imp/s at 40.7 ± 2.3 mm Hg of PO2, and Δ-5.6 ± 0.5 and Δ-5.3 ± 0.4 imp/s at 60.2 ± 3.1 mm Hg of PO2, p < 0.05, respectively) but also the CHF-induced elevation of CB chemoreceptor responses to different levels of hypoxia (Δ-13.6 ± 1.1 and Δ-13.7 ± 0.9 imp/s at 40.9 ± 3.1 mm Hg of PO2, and Δ-6.7 ± 1.2 and Δ-6.6 ± 0.8 imp/s at 59.8 ± 3.5 mm Hg of PO2, p < 0.05). In addition, mRNA and protein expressions of NADPH oxidase components (gp91phox, p40phox and p47phox) 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.
AB - Objective: A previous study from this laboratory showed that elevation of endogenous angiotensin II (Ang II) and upregulation of the angiotensin II type 1 (AT1) 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 μM (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 (Δ-12.5 ± 0.8 and Δ-12.8 ± 0.9 imp/s at 40.7 ± 2.3 mm Hg of PO2, and Δ-5.6 ± 0.5 and Δ-5.3 ± 0.4 imp/s at 60.2 ± 3.1 mm Hg of PO2, p < 0.05, respectively) but also the CHF-induced elevation of CB chemoreceptor responses to different levels of hypoxia (Δ-13.6 ± 1.1 and Δ-13.7 ± 0.9 imp/s at 40.9 ± 3.1 mm Hg of PO2, and Δ-6.7 ± 1.2 and Δ-6.6 ± 0.8 imp/s at 59.8 ± 3.5 mm Hg of PO2, p < 0.05). In addition, mRNA and protein expressions of NADPH oxidase components (gp91phox, p40phox and p47phox) 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.
KW - Angiotensin
KW - Autonomic nervous system
KW - Chemoreceptor
KW - Heart failure
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=34447523496&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34447523496&partnerID=8YFLogxK
U2 - 10.1016/j.cardiores.2007.04.006
DO - 10.1016/j.cardiores.2007.04.006
M3 - Article
C2 - 17499230
AN - SCOPUS:34447523496
SN - 0008-6363
VL - 75
SP - 546
EP - 554
JO - Cardiovascular Research
JF - Cardiovascular Research
IS - 3
ER -