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Role of NADPH oxidase‐derived superoxide anion on angiotensin II‐enhanced sensitivity of potassium channels to hypoxia in carotid body of congestive heart failure rabbits
Author(s) -
Li YuLong,
Schultz Harold D.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1268-b
Subject(s) - glomus cell , superoxide , nadph oxidase , chemistry , angiotensin ii , endocrinology , medicine , carotid body , angiotensin ii receptor type 1 , oxidase test , hypoxia (environmental) , receptor , reactive oxygen species , biochemistry , oxygen , enzyme , stimulation , organic chemistry
Our previous study has shown that endogenous angiotensin II (Ang II) via AT 1 receptor activation is involved in the enhanced sensitivity of K + currents (I K ) to hypoxia in carotid body (CB) glomus cells in congestive heart failure (CHF)(J Physiol, 575:–227; 2006). A significant body of evidence indicates that NADPH oxidase‐derived superoxide anion mediates the effects of Ang II. We investigated whether NADPH oxidase‐derived superoxide anion is a mediator of this Ang II effect in CB glomus cells, using the conventional whole‐cell patch clamp technique. Ang II augmented the effect of hypoxia on I K (46.2 ± 4.1% inhibition vs 22.5 ± 3.9% inhibition in control) and L158,809 (1 μM, AT 1 receptor antagonist), phenylarsine oxide (2 μM, PAO, NADPH oxidase inhibitor) and tempol (1 mM, superoxide scavenger) significantly blunted the effect of Ang II on sensitivity of I K to hypoxia in CB glomus cells from sham rabbits (21.7 ± 3.4%, 21.3 ± 2.7%, 20.6 ± 2.9% inhibition vs 46.2 ± 4.1% inhibition for Ang II alone, p<0.05). In CHF rabbits, the effect of hypoxia on I K in CB glomus cells was greater (53.5 ± 4.4% inhibition) than sham, and L158, 809, PAO and tempol markedly decreased the hypoxic inhibition of I K (27.7 ± 3.8%, 27.2 ± 3.2%, 26.9 ± 3.5% inhibition, p<0.05). These results indicate that the NADPH oxidase‐superoxide anion contributes to the Ang II‐enhanced sensitivity of K + channels to hypoxia in CB glomus cells from CHF rabbits.