Elevated angiotensin II attenuates activation of voltage‐gated sodium channels in heart failure rats: involvement of mitochondria‐derived superoxide

Abstract

Our previous study has shown that chronic heart failure (CHF) reduces expression and activation of voltage‐gated sodium (Nav) channels in baroreceptor neurons, which are involved in the blunted baroreceptor neuron excitability and contribute to the impairment of baroreflex in CHF state. Here we examined whether angiotensin II (Ang II) mediates CHF‐induced hypoactivation of Nav channels via mitochondria‐derived superoxide. Ang II concentration, expression of angiotensin II type I (AT1) receptors, and superoxide production were higher in nodose neurons from CHF rats than that from sham rats. Activity of manganese superoxide dismutase (MnSOD) was reduced in nodose neurons of CHF rats. Whole cell patch clamp data showed that Nav current density in baroreceptor neurons from CHF rats was lower than that from sham rats. L158,809 (AT1 receptor antagonist, 1 μM) and adenovirus MnSOD gene transfer (1 × 1010 pfu/ml) significantly increased Nav current density in baroreceptor neurons from CHF rats but not from sham rats. These results indicate that endogenous Ang II‐mitochondrial superoxide contributes to the Nav channel dysfunction of the baroreceptor neurons in CHF.