Adjacent expression of renin and angiotensinogen in the rostral ventrolateral medulla using a dual-reporter...

All components of the renin-angiotensin system are localized in the brain. However, because renin is present in very low concentrations, the mechanism by which angiotensin II is formed in the brain remains unclear. We previously reported the development of 2 transgenic mouse models using sensitive reporters, enhanced green fluorescent protein (eGFP) and beta-galactosidase (beta-Gal), to examine the cellular localization of renin and angiotensinogen in the mouse brain. To determine whether renin and angiotensinogen are coexpressed or present in neighboring cells in the rostral ventrolateral medulla (RVLM) and other cardiovascular control regions of the brain, we produced and examined double-transgenic mice, which express eGFP driven by the renin promoter (REN-1c/eGFP) and beta-gal driven by the human angiotensinogen promoter (hAGT/beta-gal). Using these reporter transgenes as sensitive markers for renin and angiotensinogen expression, we conclude that both proteins are coexpressed in the parabrachial nucleus and central nucleus of the amygdala and are in adjacent cells in the RVLM, reticular formation, bed nucleus of the stria terminalis, subfornical organ, and CA1-3 region. These data suggests that, in these areas, both renin and angiotensinogen are in close proximity providing the potential for the local formation of angiotensin I either intracellularly, when there is colocalization, or in the interstitium, when they are in juxtaposed cells.