Angiotensin II‐induced inhibition of sodium currents in aortic baroreceptor neurons mediates blunted arterial baroreflex sensitivity in heart failure rats (1169.3)

Abstract

Impairment of arterial baroreflex sensitivity (ABS) is associated with increased mortality in patients with chronic heart failure (CHF). Increase in plasma angiotensin II (Ang II) level is often seen in CHF and contributes to the baroreflex dysfunction. Our previous studies have confirmed that reduced expression of voltage‐gated sodium (Nav) channels in aortic baroreceptor (AB) neurons is involved in attenuation of the ABS in CHF rats. In this study, we investigated acute effect of Ang II on Nav currents in AB neurons and on the ABS from sham and CHF rats. Using Ang II 125I radioimmunoassay, real‐time PCR and western blot, we found that Ang II level, mRNA and protein expression of Ang II type 1 (AT1) receptor in nodose ganglia (NG) from CHF rats were higher than that from sham rats. Data from whole cell patch‐clamp recording showed that Ang II (100 nM) acutely inhibited Nav currents in A‐ and C‐type AB neurons from sham and CHF rats. AT1 receptor antagonist losartan (1 µM) totally abolished the effect of Ang II on Nav currents. In addition, the inhibitory effect of Ang II on Nav currents was larger in CHF rats than that in sham rats. Local microinjection of Ang II (0.2 nmol) into the NG decreased the ABS in sham rats. However, local losartan (1 nmol) improved the blunted ABS in CHF rats. These results suggest that elevated endogenous Ang II in the NG contributes to the impaired ABS in CHF rats through inhibiting Nav channels.Grant Funding Source: Supported by National Heart, Lung, and Blood Institute grant HL‐098503 (to Y.‐L.L.)