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

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.