Aminopeptidase A

Abstract

Several decades of investigation have provided unequivocal support for the existence of an intrinsic brain renin-angiotensin (Ang) system (RAS) and its involvement in the control of cardiovascular functions.1,2 Essential components of the RAS, ie, renin, angiotensinogen, Ang-converting enzyme, Ang-converting enzyme 2, type 1 Ang II, and type 2 Ang II receptors, as well as various aminopeptidases, are synthesized within the brain, and the hyperactivity of RAS in the brain is implicated in the development and maintenance of hypertension.1,2 Moreover, interruption of the brain RAS activity by either pharmacological or genetic means is associated with a profound beneficial outcome in hypertension.1,2 Thus, the brain RAS may be an important target for hypertension with neurogenic origin. Many years ago it was proposed that the physiologically relevant peptide in the brain RAS that regulates blood pressure (BP) is Ang III rather than Ang II.3,4 Ang III, also called Ang-(2-8), is generated from Ang II by aminopeptidase A (APA), which cleaves the Asp1-Arg2 bond in Ang II. Persuasive evidence have been presented in support of this “Ang III hypothesis”: (1) Ang III, when centrally administrated, enhances BP; stimulates vasopressin release, thirst, and sodium appetite; and decreases baroreceptor reflex function3,5,6; (2) Ang III displays comparable affinity to Ang II for the type 1 Ang II receptor3; (3) specific inhibitors of APA …