**3. Brain APA**

Aminopeptidase A (APA) is a 109 kDa homodimeric zinc-metallopeptidase that catalyzes the cleavage of glutamatic and aspartatic amino acid residues from the N-terminus of polypeptides. It is encoded by the ENPEP gene and is also known as glutamyl aminopeptidase, gp160, or CD249.

Numerous studies have demonstrated the major role of brain AngIII and both APA and APN in the control of BP and in arterial hypertension [26]. Thus, the intracerebroventricular (icv) injection of APA to induce the transformation of AngII into AngIII was found to elevate BP in normotensive WKY and SHR animals [27]. In contrast, the icv administration of APN, which hydrolyzes AngIII, reduced the BP in WKY rats and to a greater degree in SHR animals [28]. A study of the icv administration of analogs of AngII and AngIII to SHR rats found that a greater BP increase was induced by AngIII than with AngII [29], thus indicating that a major BP reduction is produced by the inhibition of APA activity and consequent interference in the transformation of AngII to AngIII [30], which suggests a greater contribution of brain AngIII than AngII to the BP increase (Figure 2).

**Figure 2.** Systemic aminopeptidase A (APA) and aminopeptidase N (APN) in blood pressure control.
