C-Fos activation in renal hypertension

Hypertension is a common sequelae of renal disease. Both the renin angiotensin system (RAS) and neural sensory inputs from the kidney may play a role in this process by driving the activity of brain regions associated with hormonal and sympathetic nervous system output. We aimed to determine if different types of renal hypertension show differential activation of key brain areas. We compared central c-fos expression in 3 models of renal hypertension driven by distinct mechanisms (i) two-kidney one clip (2K1C, n=6; humoral RAS model), (ii) phenol renal injury (n=3; renal sensory afferent model) and (iii) genetic polycystic kidney disease (PKD) in a Lewis strain (LPK, n=8, chronic renal failure model). We predict that in the LPK, hypertension is driven by both humoral RAS and renal afferent pathways. Activated neurons were identified using Fos-like immunoreactivity (FLI) in the brainstem, hypothalamus and circumventricular organs from the models and control Lewis rats (n=8). After blood pressure recordings, animals were euthanased at 18 weeks and perfused with 4 % formalin. Coronal sections (50μm) of the rostral ventro-lateral medulla (RVLM), nucleus of the solitary tract (NTS); organum vasculosum of the lamina terminalis (OVLT), subfornical oragan (SFO); supraoptic nucleus (SON) and paraventricular nucleus (PVN) were prepared. Immunohistochemistry was performed using an avidin-biotin peroxidase procedure. The intensity of FLI in each brain region was examined. Mean systolic blood pressure showed significant increases in the 2K1C and renal injury models compared to control animals (P < 0.05). The increases observed in blood pressure were paralleled by higher FLI in the brain regions examined, except for the absence of FLI in the SFO region of the renal injury model. Mean blood pressure for the LPK was significantly higher compared to all other groups (P < 0.0001). In the LPK, FLI was detected at higher levels in all brain areas studied, again paralleling the significantly greater blood pressure. This data suggests that in LPK rats, both the renal afferents and RAS play a role in driving increased CNS activity. The absence of FLI in the SFO of the renal injury model, and the specific neuronal populations activated in each model are yet to be elucidated.