Overexpression of apelin in the paraventricular nucleus increases blood pressure and sympathetic nerve activity in normotensive rats

Abstract

Studies of the peripheral apelin/APJ receptor system indicate that it plays a significant role in cardiovascular regulation. Here, we determined the in vivo actions of apelin in the paraventricular nucleus (PVN) on the central regulation of blood pressure (BP) and sympathetic outflow. Microinjection of exogenous apelin‐13 into the PVN caused dose‐dependent increases in mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA). To further ascertain the role of apelin in PVN, we overexpressed apelin within PVN by AAV2 vector‐mediated gene transfer. Western blot analysis showed that microinjection of AAV2‐apelin into the PVN resulted in a significant increase in apelin expression and that overexpression of intrinsic apelin caused chronic BP elevation and a significant increase in plasma norepinephrine levels. In addition, APJ receptors were localized in RVLM projecting PVN neurons using an immunofluorescent retrograde labeling approach and superfusion of these neurons with exogenous apelin‐13 significantly increased neuronal firing activity, which was measured with whole‐cell patch clamp recording in current‐clamp mode. In summary, the data demonstrate that the apelin/APJ receptor system in the PVN may play an important role in the regulation of sympathetic outflow and in the central control of BP.