The Renin-Angiotensin-Aldosterone System (RAAS)

The Renin-Angiotensin-Aldosterone System is activated when we experience a drop in arterial pressure. It is especially important when we suffer cardiac issues. When it is activated it produces a number of responses that produce an increase in arterial pressure to bring it back to a normal level. We look at each component in turn.

Renin

Renin is the enzyme secreted by the juxtaglomerular cells of the kidneys into the bloodstream. The enzyme is synthesized from a pre-prohormone called pre prorenin which has no biological activity in its own right. Renin is generated from pro-renin in the kidneys. The enzyme is also produced in women from their ovaries. Renin converts the pro-enzyme angiotensinogen into angiotensin I.

Angiotensinogen

Angiotensinogen is synthesized in the liver where it circulates throughout the blood plasma. It is removed by the endoplasmic reticulum. It is the precursor of angiotensin I and thus angiotensin II. Angiotensin I is a decapeptide.

Angiotensin Converting Enzyme (ACE)

Angiotensin Converting Enzyme (ACE) is one of the most important enzymes in this system. It converts angiotensin I into angiotensin II. This enzyme is located in the endothelial cells and the conversion usually occurs  when blood passes through the lungs although it also happens in other organs too especially the kidneys.

ACE is a zinc protease which requires zinc and chloride to activate it too. 

The Mechanism of the RAAS

The RAAS  process is designed to regulate arterial pressure by regulating blood volume. It is a strongly hormone regulated system. Any reduction in arterial blood pressure produces a drop in the renal perfusion pressure which then triggers the conversion of pro-renin into renin. Plasma borne renin then acts on angiotensinogen and the process of conversion of components progresses onwards.

When angiotensin II is produced from angiotensin I, it acts on the zona glomerulosa cells in the adrenal cortex to stimulate the production and synthesis of the hormone aldosterone. 

Aldosterone increases the reabsorption of sodium ions by activating on particular cells of the renal distal tubule and the collecting ducts. Blood volume increases because water is reabsorbed as sodium ions are reabsorbed through the power of osmosis.

Angiotensin II is also a potent vasoconstrictor by acting on arterioles to produce vasoconstriction which produces an increase in total peripheral resistance hence and increase again in arterial pressure. It also works on the hypothalamus to increase thirst and thus water intake to help raise blood volume. The additional effect is to stimulate anti-diuretic hormone which also increases water reabsorption in the collecting ducts. ACE incidentally inactivates the catalytic activity of bradykinin.

ACE then is a key target for blood pressure treatment (Ondetti et al., 1977). There are many different peptides which comes from different food sources that all inhibit ACE. The sources include milk casein (Karaki et al., 1990), soy sauce (Kinoshita et al., 1993), soybean, cheese whey (Yamamoto et al., 1994; Amhar et al., 1996; Abubakar et al., 1998), various fish sources including Alaskan Pollock, and zein (Miyoshi et al., 1991).

All these changes in activity lead to a return to blood pressure.

References

Abubakar, A., Saito, T., Kitazawa, H., Kawai, Y. & Itoh, T. (1998). Structural analysis of new antihypertensive peptides derived from cheese whey protein by proteinase K digestion. Journal of Dairy Science, 81, pp. 3131–3138.

Amhar, A., Saito, T., Aimar, M.V. & Itoh, T. (1996). New derivation of the inhibitory activity against angiotensin converting enzyme (ACE) from sweet cheese whey. Tohoku Journal of Agricultural Research (Japan), 47, pp. 1–8

Karaki, H., Doi, K., Sugano, S. et al. (1990). Antihypertensive effect of tryptic hydrolysate of milk casein in spontaneously hypertensive rats. Comparative Biochemistry and Physiology, 96, pp. 367–371

Kinoshita, E., Yamakoshi, J. & Ikuchi, M. (1993). Purification and identification of an angiotensin I-converting enzyme inhibitor from soy sauce. Bioscience, Biotechnology, and Biochemistry, 57, pp. 1107–1110. 

Miyoshi, S., Ishikawa, H., Kaneko, T., Fukui, F., Tanaka, H. & Maruyama, S. (1991). Structures and activity of angiotensin-converting enzyme inhibitors in an a-zein hydrolysate. Agricultural and Biological Chemistry, 55, pp. 1313–1318. 

Ondetti, M.A., Rubin, B. & Cushman, D.W. (1977). Design of specific inhibitors of angiotensin converting enzyme: a new class of orally active antihypertensive agents. Science, 196, pp. 441–444

Yamamoto, N., Akino, A. & Takano, T. (1994). Antihypertensive effect of the peptides derived from casein by an extracellular proteinase from Lactobacillus helveticus CP790. Journal of Dairy Science, 77, pp. 917–922. .