## 1 Introduction  
Blood pressure depends on the interaction of several factors, integrated and coordinated through the central nervous system. These factors include peripheral vascular resistance [1], the circulating blood volume [2,3], blood viscosity [4], and the elasticity of arterial walls [5,6]. The circulatory system has an extensive mechanism for controlling blood pressure. For instance, if at any given time the pressure significantly deviates from its normal mean value, nervous reflexes are triggered within seconds, causing changes that restore the pressure to normal levels [7,8]. Over longer periods, the kidneys play a crucial role in pressure control by secreting hormones that regulate it. The renin-angiotensin system (RAS) is perhaps the most important and powerful endocrine system affecting blood pressure control. It is an automatic feedback mechanism that helps maintain blood pressure at a normal or near-normal level. It is considered the potential pathway for the synthesis of angiotensin II (AngII), which is responsible for both the short-term and long-term control of blood pressure [9; 10; 11; 12; 13; 14]. In this system, renin, an enzymatic protein secreted by the kidney into the bloodstream when one's blood pressure drops too low, helping to increase blood pressure in several ways, acts on the peptide chain of its substrate, angiotensin, producing angiotensin I (AngI), an inactive decapeptide that has only weak vasoconstrtive properties, which are insufficient to cause significant functional alterations in circulatory function. Therefore, AngI serves primarily as a precursor to AngII. AngI is further processed by angiotensin-converting enzyme (ACE), which generates one of the most active peptides of the system, AngII, as blood passes through the endothelium of the pulmonary vessels. AngII induces arteriolar constriction and increases blood pressure. It is one of the most potent vasoconstritors known, but its pressor activity is diminished in individuals with sodium depletion and in patients with cirrhosis and other diseases [15; 16]. In these cases, circulating AngII increases, but its activity is regulated by a reduction in AngII receptors in vascular smooth muscle, resulting in a diminished response to AngII. AngII is rapidly destroyed, with a half-life of one to two minutes. The enzymes that degrade AngII are collectively referred to as angiotensinases. They include aminopeptidase A (APA) and aspartyl aminopeptidase (ASAP), which form a heptapeptide known as angiotensin III (AngIII), which also possesses biological activity. AngIII is further processed by other enzymes, such as aminopeptidase N and/or B (APN, APB), yielding angiotensin IV (AngIV), which also has biological activity [11; 13; 17; 18; 19; 20; 21]. Although RAS functions as an endocrine system that regulates blood pressure by acting on peripheral resistance and sodium excretion, it also functions as an autocrine-paracrine system with important local tissue effects. The current understanding is that circulating RAS is not directly responsible for increased blood pressure in essential hypertension. In fact, many hypertensive patients have low levels of renin and AngII, and drugs that block the RAS are not particularly effective in such cases. However, there is growing evidence supporting the role of local tissue RAS in controlling blood pressure. Studies have shown that, in addition to systemic AngII production, many tissues have the ability to generate AngII locally, apparently for local use. Tissue RAS components have been identified in the walls of blood vessels, the adrenal cortex, testicles, the anterior and intermediate lobes of the pituitary gland, the brain, kidneys, and other organs. The role of these tissue RAS systems is not yet fully understood; however, it is known that tissue-derived renin contributes very little to the pool of circulating renin, as plasma renin activity nearly disappears when the kidneys are removed [8; 18; 19; 20; 21].