Identity of angiotensinogen precursors of rat brain and liver

Angiotensin modifies a number of functions of the central nervous system (CNS) including blood pressure regulation, thirst, and the secretion of the antidiuretic and adrenocorticotropic hormones. Whereas peripheral administration of angiotensin produces these effects, accumulating evidence implicates a brain angiotensin system which operates independently of the circulating renin-angiotensin system (reviewed in refs 1-3). All components of the renin-angiotensin system have been identified in the brain, but there is considerable controversy over whether these components are synthesized in the brain or derived from plasma and the extent to which these components interact to generate angiotensin in the brain in vivo. Whereas many different enzymes are able to cleave angiotensinogen (renin substrate) to release angiotensin I (AI) or angiotensin II (AII), angiotensinogen is the only known precursor of AI and AII. Definitive evidence for an independent brain angiotensin system requires the demonstration that the brain synthesizes an angiotensin precursor. Here we report the identification of angiotensinogen mRNA in rat brain by cell-free translation and show that the brain angiotensinogen precursors are identical to those previously identified for liver, the source of plasma angiotensinogen.