Our experimental model is the angiotensinII (AngII)-salt model.
As illustrated in the figure to the right, we propose that moderate elevations in AngII concentrations in blood increase MAP predominantly through an increase in sympathetic nerve activity (SNA). This occurs as a result of synergistic actions of dietary salt and AngII in the brain. Specific brain targets are neurons in the area postrema (AP), subfornical organ (SFO), and possibly other circumventricular organs. These neurons link to the major descending bulbospinal pathways in the rostral ventrolateral medulla (RVLM) by way of hypothalamic (e.g., paraventricular nucleus (PVN)) and brainstem circuits whose anatomical and neurochemical organization remain to be fully defined. Sustained increases in SNA depend in part on time-dependent alterations in the central pathways mediating RVLM activation. Represented are the 4 major groups to be studied. Stylized pathways represent hypothesized changes in the activity of central pathways over time in the AngII+HNa group. During the transient phase, MAP is increased by non-neural mechanisms and SNA may actually be decreased to some vascular beds by baroreflexes. However, by steady-state sustained elevation of AngII activates hypothetical pathways that drive the RVLM and SNA. Overall activity levels are indicated by color ranging from dark blue (lowest) to orange (highest).
