**2. Aminopeptidases in Arterial Hypertension**

A list of the most common aminopeptidases with their enzyme commission (EC) numbers and their main abbreviations is shown in Table 1. As was introduced in the previous paragraph, aminopeptidases (Aps) generate the active compounds of the RAS and play an essential role in BP control and sodium handling [9]. APs can also degrade certain peptidergic hormones or neuropeptides such as vasopressin, cholecystokinin, and enkephalins [10]. For this reason, APs have been analyzed in plasma, kidney, and other tissues related to BP control in several rat models of hypertension.


**Table 1.** Types of aminopeptidases showing their most common abbreviations.

Thus, reduced renal membrane-bound APA, iRAP, and APN activities were observed in a reduced renal mass saline model, and reduced APA activity was detected in a two-kidney one-clip Goldblatt hypertension model [11]. In the low renal mass model, a positive correlation was found in both soluble CAP and APN activities between the neurohypophysis and the adrenal gland, but this was not observed in the normotensive rats [12].

The relationship between APs and arterial hypertension has been explored with greater precision. For instance, it has been proposed that endoplasmic reticulum AP 1 (ERAP1) and ERAP2 regulate BP by inactivation of AngII, and these two APs, which also hydrolyze amino acids from the N-terminus of various human antigens and peptide hormones, are widely expressed in human tissues, including heart, endothelial cells, and kidney [13–15]. In vitro, ERAP1 transforms AngII into AngIII and AngIV [14], while ERAP2 converts AngIII to AngIV [15]. ERAP 1 was initially identified as a placental leucine AP that degrades AngII and III and transforms kallidin into bradykinin in vitro, thus has a role in BP regulation [14].

In this sense, several interesting papers have been published. In an in vivo study, an increase in circulating levels of ERAP1 was found to reduce BP and AngII levels [16]. In a genetic study, an association was detected between variants of the gene encoding Arg528 and the development of essential hypertension in a Japanese population [17]. In an investigation of 45 genetic variants of ERAP1 and ERAP2 in 17,255 Caucasian females from the Women's Genome Health Study, ERAP1 was found to be related to increased BP [18]. The ERAP1 genotype also appears to be involved in the reduction of left ventricular mass produced by some antihypertensive treatments [19]. Thus, all these data indicate a possible role for ERAP1 in BP regulation and ventricular remodeling. Finally, other genetic studies have associated variants of ERAP1 and ERAP2 genes with preeclampsia [20], hemolytic uremia [21], and hypertension [17].
