**10. References**


**5** 

*Brazil* 

Roberto de Barros Silva

**Hypertension and Renin-Angiotensin System** 

The renin-angiotensin system (RAS) participates in numerous biological activities. Among these is the pathophysiological mechanisms of hypertension, congestive heart failure, myocardial infarction, diabetic nephropathy and inflammatory disorders. These pleiotropic effects led to the development of new therapeutic approaches to inhibit the actions of this system. This chapter aims to relate the inflammatory process with the RAS thus focusing on the effects of antihypertensive drugs in the therapeutic and / or prevention of pathophysiological conditions. Also discussed in this chapter also the pharmacodynamic of ACE inhibitors, ARB inhibitors and Direct Renin Inhibitors, as well as a review of the RAS. For a better knowledge of the system, it is necessary to first discuss the history of RAS

components and focusing on general biochemistry, cell biology in its overall effects.

The RAS is classically known as a circulatory system or hormone that regulates blood pressure and homeostasis of electrolytes and fluids. This classic study is originated from 1898 when Tiergersted and Bergman found that the kidney contained a pressor substance, through non-purified salt extracts, which was called renin. This discovery came only to attract attention with Goldblatt et al in the twentieth century in 1934 when they demonstrated that the constriction of the renal arteries producing persistent hypertension in dogs due to reduction in vascular area with a consequent increase in strength and blood pressure (Goldman and Gilman, 2007). Six years later he declared that the renin was actually a protein that acted on a substrate in plasma. The name of this substrate for 20 years was controversial, as two groups of researchers, one from Argentina and other U.S. called them differently. The first group was called the substrate of *hipertensin* and the second *angiotonin* until these names were changed to *angiotensin*, the true pressor material. The precursor of this peptide was called angiotensinogen. Therefore, the time had an idea this simplified

In the 50's has been identified two forms of angiotensin, respectively called of angiotensin I and II. The first would be a chain of 10 peptides, hence the term decapeptide. In contrast, the second would be formed by cleavage of two peptides of angiotensin I to form an octapeptide. This cleavage occurs through the participation of an enzyme located on the luminal surface of endothelial cells of vascular system known as Angiotensin Converting

**1. Introduction** 

system, Figure 1.

**2. Renin-angiotensin system** 

*Pharmaceutical Sciences Faculty of Ribeirao Preto FCFRP/USP, São Paulo,* 

