Angiotensin II enhances hyperpolarization-activated currents in rat aortic baroreceptor neurons: involvement of superoxide

Abstract

As an endogenous physiologically active peptide, angiotensin (ANG) II plays an important role in the maintenance of blood pressure. In the arterial baroreceptor reflex (a pivotal regulator of blood pressure), aortic baroreceptor (AB) neurons located in the nodose ganglia (NG) are a primary afferent limb of the baroreflex. Hyperpolarization-activated currents ( Ih) in the AB neurons contribute to the excitability of the AB neurons. Therefore, the present study was to measure the modulating effect of ANG II on the Ih in the primary AB neurons isolated from rats. Data from immunofluorescent and Western blot analyses showed that protein of AT1 and AT2 receptors was expressed in the nodose neurons. In the whole cell patch-clamp recording, ANG II concentration dependently enhanced the Ih density in the AB neurons (100 nM ANG II-induced 53.8 ± 3.8% increase for A-type AB neurons and 30.4 ± 7.7% increase for C-type AB neurons at test pulse −140 mV, P < 0.05). ANG II also decreased membrane excitability in the AB neurons. AT1 receptor antagonist (1 μM losartan) but not AT2 receptor antagonist (1 μM PD-123,319) totally abolished the effect of ANG II on the Ih and neuronal excitability. In addition, NADPH oxidase inhibitor (100 μM apocynin) and superoxide scavenger (1 mM tempol) also significantly blunted the ANG II-induced increase of the Ih and decrease of the membrane excitability in the AB neurons. Furthermore, losartan, apocynin, or tempol significantly attenuated the superoxide overproduction in the NG tissues induced by ANG II. These results suggest that ANG II-NADPH oxidase-superoxide signaling can activate the Ih and subsequently decrease the membrane excitability of rat AB neurons.