## 4 Discussion
### RAS-Regulatory Enzymes
#### 4.5.2 On the Regulatory Enzymes of the RAS in the Hypothalamic-Pituitary-Adrenal Axis  
The hypothalamic-pituitary-adrenal (HPA) axis is an important regulator of blood pressure and fluid and electrolyte homeostasis. In addition to the circulating RAS, local systems have been described in the brain, pituitary, and adrenal glands. These local RASs have been implicated in the central regulation of the cardiovascular system and body water balance, the secretion of pituitary hormones, and the secretion of aldosterone by the adrenal glands. However, it has been shown that their function is very different in males and females [19; 66; 69; 105; 106]. In any case, all the animals used in the present study were males. In the hypothalamus, changes in ACE activity are observed in WKY animals with moderate NAB intake and non-moderate AB intake. These results are not repeated in SHRs. On the other hand, alterations in the ASAP, APB, and APN activities are observed in different directions depending on the experimental group and whether they are WKY or SHRs. Meanwhile, there are no changes in APA activity. The existence of many hypothalamic nuclei involved in neuroendocrine regulation through the RAS is well known [19; 19; 66; 107; 108; 190]. With these data, the existence of compensatory mechanisms for maintaining blood pressure is shown; on the one hand, this is to regulate the high volume of liquid ingested with NAB, and on the other, to regulate the alcohol ingested with AB. It can be said that these mechanisms are different in WKY and SHRs, or that SHRs do not have them, which would be responsible for the hypertension shown by these animals. Beer does not decrease blood pressure levels in SHRs, and it does not increase levels in WKY animals. At the pituitary level, both anterior and intermediate posterior, the most notable changes occur in the APA, ASAP, APB, and APN activities, while the ACE activity does not show significant alterations. Regarding the ASAP and APA activities, a decrease is observed with NAB in WKY animals and an increase is observed in SHRs with moderate NAB intake. Likewise, the mechanisms that regulate the body fluid volume differ in both groups, with beer not having the capacity to modify blood pressure in any of the groups. The APB and APN activities are similar, with small variations in SHRs, where the activities increase with both NAB and AB. These changes in RAS regulatory activities would imply alterations in different directions in the levels of the different angiotensins. It should be noted that pituitary angiotensins are involved in the processes that regulate the synthesis and release of a wide variety of hormones, such as vasopressin or antidiuretic hormone [19; 19; 106; 110], also involved in the regulation of blood pressure. Therefore, beer consumption will modify these regulatory mechanisms at the pituitary level, which, as we have noted, will act differently in WKY and SHRs, probably with the same purpose but through different mechanisms. This is in order to avoid the increase in blood pressure in WKY and SHRs induced by the increase in blood volume or alcohol consumption. Beer also does not have the necessary capacity to decrease blood pressure with the modifications that take place at the level of pituitary hormonal regulation. In the adrenal glands, the pattern of RAS regulatory enzyme activity is similar. Thus, no changes are observed in ACE activity, and few are observed in the APA and ASAP activities at the adrenal cortex level; meanwhile, significant changes appear in the APB and APN activities, both at the cortex and adrenal medulla levels, and in ASAP and APA at the medulla level. These changes consist of a decrease with AB intake in WKY animals in the soluble fraction and an increase with NAB intake in WKY animals in the membrane fraction. No modifications are observed in the soluble fraction in SHRs, but they are in the membrane fraction and in the same direction as the previous ones. As for APN, it is decreased in WKY animals with AB or NAB intake and increased in SHRs with AB.