Abstract 114: Selective Activation of the Renin-Angiotensin System in the Subfornical Organ is Sufficient to Elicit Fluid and Sodium Intake Behaviors
Increased activity of the renin-angiotensin system (RAS) within the brain results in polydipsia and hypertension, and various lines of evidence suggest that the subfornical organ (SFO) is an important region mediating these effects. We sought to verify a model of spatially- and temporally-inducible angiotensin (ANG) production, and to determine the sufficiency of ANG production within the SFO to elicit polydipsia and sodium intake. Mice expressing human renin via the neuron-specific promoter, synapsin (sR mice), were bred with mice expressing an inducible human angiotensinogen (hAGT) gene via the ubiquitous CAG promoter (A-Red mice) to generate sRA-Red mice. Exposure of the A-Red construct to Cre-recombinase results in excision of a dsRed reporter gene, and induction of hAGT expression. An adenovirus encoding Cre and GFP (AdCre) was injected into the lateral cerebral ventricle (ICV) of sRA-Red mice or control littermates (NT) to target the SFO. At baseline, fluid (NT: 0.18±0.03 vs sRA-Red: 0.19±0.04 mL/g/day) and sodium intakes (NT: 0.53±0.11 vs sRA-Red: 0.74±0.21 mEq/day) were similar between NT and sRA-Red mice. After 21 days sRA-Red mice receiving AdCre exhibited polydipsia (NT: 0.24±0.02 vs sRA-Red: 0.40±0.04 mL/g/day, P<0.05) and increased sodium intake (NT: 0.88±0.05 vs sRA-Red: 1.59±0.19 mEq/day, P<0.001). We validated SFO-specific targeting using a ROSA-TdTomato reporter mouse line. Cre-mediated recombination persisted in the SFO for at least 60 days after injection. Together, these data support the hypothesis that SFO-specific hyperactivity of the RAS is sufficient to cause polydipsia and sodium intake. We are currently investigating the effect on arterial pressure.
- © 2012 by American Heart Association, Inc.