## 4 Discussion
### RAS-Regulatory Enzymes
#### 4.5.3 On the Regulatory Enzymes of the RAS in the Kidney  
At the renal level, limited changes in ACE activity are observed both at the cortical and medullary levels. Regarding cortical or medullary ASAP activity, the intake of alcoholic or non-alcoholic beer causes a decrease in this activity in WKY animals, while in SHRs, it causes an increase. APA activity shows a decrease in WKY animals with alcoholic beer and an increase with non-alcoholic beer. On the other hand, in SHRs, it increases with the intake of either type of beer. The APN and APB activities are only affected at the cortical level, where they increase with alcoholic beer and decrease with non-alcoholic beer in WKY animals; meanwhile, in SHRs, they increase with alcoholic beer. Again, there are changes in the angiotensin levels at the renal level, which varies depending on the type of beer ingested and the group of animals considered. It has been previously mentioned that in the long term, most actions leading to hypertension may be balanced or compensated by the renal and body fluid systems. Thus, if pressure increases, the renal excretion of water doubles, and sodium excretion occurs. It is more likely that pressure increases due to salt intake rather than water, as water is excreted almost as it is ingested. Therefore, if the regulatory mechanisms of water and sodium excretion maintain the balance of fluids and sodium, normal blood pressure can be maintained [111; 112; 113; 114]. The modifications in RAS regulatory enzymes in the present study, which vary depending on the type of beer ingested and the group of animals considered, are related to the absence of modifications in blood pressure levels. This, again, confirms or supports the idea that all changes produced in the regulatory enzymes of the RAS after beer intake are the result of compensation and the balance of fluids and electrolytes to maintain the pressure levels in each group through different mechanisms. 4.5.4. On the Regulatory Enzymes of the RAS in the Lung  
Although the alterations described so far in ACE have been minimal, the pulmonary activity of this enzyme is profoundly affected in the different experimental groups considered in this study. Thus, ACE increases with the intake of alcoholic or non-alcoholic beer in both WKY and SHRs. However, both APA and ASAP activity decrease only in WKY animals with the intake of either type of beer, while in SHRs, the APN activity is altered, and also decreased. This implies that ACE in the lung is the main factor responsible for maintaining blood pressure in these groups of animals and responds in the same direction to the different agents that induce hypertension. As mentioned, it is the conversion of angiotensin I to angiotensin II that occurs in the pulmonary vessels [115]. However, ACE is an enzyme that also has an affinity for other substrates, such as bradykinin (vasodilator) [116], and the resulting activity will be the consequence of the combined actions on its different substrates [105]. On the other hand, as in other tissues, the existing differences in other enzymatic activities between WKY and SHRs demonstrate the existence of mechanisms that act differently in both groups of animals to control blood pressure. To summarize the results concerning the modulation of the RAS, significant changes in RAS enzyme activity have been found in several tissues, including the hypothalamic-pituitary-adrenal (HPA) axis, the kidneys and the lungs. Changes in the HPA axis indicate that beer consumption may influence neuroendocrine regulation. Changes in the kidneys suggest that beer consumption may affect the renal mechanisms involved in long-term blood pressure control. In the lungs, changes in angiotensin-converting enzyme (ACE) activity suggest that beer may influence the conversion of AngI to AngII. Some future clinical implications that could be explored are the effects of beer consumption in individuals with a genetic predisposition to hypertension.