Superoxide anions modulate the effects of angiotensin-(1-7) in the rostral ventrolateral medulla on cardiac sympathetic afferent reflex and sympathetic activity in rats

Abstract

Both angiotensin (Ang)-(1-7) and Ang II in the rostral ventrolateral medulla (RVLM) increase renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) and enhance the cardiac sympathetic afferent reflex (CSAR). NAD(P)H oxidase-derived superoxide anions in the RVLM mediate the effects of Ang II on CSAR and sympathetic activity. However, whether the superoxide anions mediate the effects of Ang-(1-7) in RVLM is still unclear. This study was designed to determine whether superoxide anions mediate the effects of Ang-(1-7) in the RVLM, including increasing the RSNA and MAP and enhancing the CSAR, and to determine whether NAD(P)H oxidase is the major origin of the superoxide anions in rats. RSNA and MAP were recorded in sinoaortic-denervated and cervical-vagotomized rats with urethane and α-chloralose anesthesia. The CSAR was evaluated by the RSNA and MAP responses to the epicardial application of capsaicin. Bilateral RVLM microinjection of the superoxide anion scavengers tempol or tiron, or the NAD(P)H oxidase inhibitor apocynin inhibited the effects of Ang-(1-7) in RVLM, while the superoxide dismutase (SOD) inhibitor diethyldithiocarbamic acid (DETC) potentiated the effects of Ang-(1-7). Ang-(1-7) increased but Mas receptor antagonist D-Alanine-Ang-(1-7) (A-779) decreased the NAD(P)H oxidase activity and superoxide anion level in the RVLM. The Ang-(1-7)-induced increases in NAD(P)H oxidase activity and superoxide anion level were abolished by pre-treating the RVLM with apocynin or A-779 but not the AT(1) receptor antagonist losartan. The epicardial application of capsaicin increased NAD(P)H oxidase activity and superoxide anion level; the effect was inhibited by A-779 and enhanced by Ang-(1-7). These results indicate that superoxide anions are involved in modulating the effects of Ang-(1-7) and Mas receptor in the RVLM: increasing the RSNA and MAP and enhancing the CSAR. The enzyme of NAD(P)H oxidase is a major source of the superoxide anions that modulate the effects of Ang-(1-7) in the RVLM.