The renin angiotensin system (also known as the RAA Pathway) is a complex process that the body uses to maintain fluid, sodium and blood preasure homeostasis in the human body. If you want to learn more about homeostasis in the human body, please review my homeostasis page. Through the complex RAA pathway, the body maintains homeostasis through the use of renin, angiotensin, aldosterone and how these affect body systems such as the patients vasculature, kidney functions, and release of vasoconstricting hormones such as adrenaline.
Definitions of the enzymes, hormones, and peptides involved in the RAA Pathway and their purpose:
Renin is an enzyme that is produced by the kidneys as a negative homeostatic response to a decreased intra-renal pressure in the juxtaglomerular due to insufficient blood flow and blood
pressure. Renin is also released when the glomerular cells detect insufficient levels of sodium ions indicating a decrease in overall fluid balance.
Angiotensinogen is a peptide produced by the liver. When Angiotensinogen combines with renin the enzyme angiotensin is produced.
Angiotensin. Angiotensin is an oligopeptide found in the blood, which is capable of causing vasoconstriction, which in turn causes an increase in systemic blood pressure. Angiotenisn also
causes the adrenal cortex to release aldosterone, which is a hormone known to increase thirst (dipsogen) and reduce renal release of sodium ions, therefore increase water retention.
Angiotensin II. Angiotensin I is converted by an angiotensin converting enzyme (ACE) into angiotensin II. ACE is found in capillaries throughout the body, however, due to the high amounts of capillaries found in the lungs, the lungs have the highest concentration of ACE. Angiotensin II, III and IV increase blood pressure through a variety of biological mechanisms that
effect: the kidneys, vasculature, and hormones.
Angiotensin Converting Enzyme (ACE). ACE is an enzyme found primarily in capillaries (particularly in the lungs), which convert angiotensin I into angiotensin II. Many blood pressure medications target ACE in order to artificially regulate a person’s blood pressure. Many blood pressure medications known as ACE inhibitors block the body’s ability to produce ACE,
and therefore the body is unable to convert angiotensin I into angiotensin II, which will cause a the human body to increase its blood pressure. One of the unfortunate side effects of ACE
inhibitors is that they may reduce the moisture in a person’s lungs, and therefore increase the risk of respiratory infection and the presence of a non-productive cough.
Here is a flowchart of the RAA Pathway in action:
Angiotensin Effects on the Body
Angiotensin I has limited known effects on the human body, other than being a precursor to angiotensin II. However, angiotensin II, III
and IV have profound effects on the human body and a regulatory role in controlling a person’s blood pressure.
Angiotensin II acts to increase blood pressure through the following mechanisms:
– As a potent direct vasoconstrictor, constricting arteries and veins and increasing blood pressure. When cardiac cell growth is stimulated, a local anngiotensin
system is activated in the cardiac myocyte, which stimulates cardiac cell growth through Protein Kinase C. The same system can be activated in smooth muscle cells in conditions of hypertension, atherosclerosis, or endothelial damage.
– A1 adrenoreceptor stimulation causing vasoconstriction.
– Thirst sensation (dipsogen) through the subfornical organ (SFO) of the brain, decreases the response of the baroreceptor reflex, and increases the desire for
salt. It increases secretion of ADH in theposterior pituitary and secretion of ACTH in the anterior pituitary.
– Angiotensin II has a direct effect on the proximal tubules to increase Na+ reabsorption. It has a complex and variable effect on glomerular filtration and renal blood flow
depending on the setting. Increases in systemic blood pressure will maintain renal perfusion pressure; however, constriction of the afferent and efferent
glomerular arterioles will tend to restrict renal blood flow. The effect on the efferent arteriolar resistance is, however, markedly greater, in part due to
its smaller basal diameter; this tends to increase glomerular capillary hydrostatic pressure and maintain glomerular filtration rate. A number of other
mechanisms can affect renal blood flow and GFR. High concentrations of Angiotensin II can constrict the glomerular mesangium reducing the area for glomerular
filtration. Angiotensin II as a sensitizer to tubuloglomerular feedback preventing an excessive rise in GFR. Angiotensin II causes the local release of
prostaglandins, which, in turn, antagonize renal vasoconstriction. The net effect of these competing mechanisms on glomerular filtration will vary with
the physiological and pharmacological environment.
Angiotensin III has mild vasopressor capabilities, but almost 100% of the aldosterone producing effects on the adrenal cortex. By stimulating the adrenal cortex,
angiotensin III causes the adrenal cortex to release aldosterone. Aldosterone is a hormone that causes the kidneys to retain sodium and lose potassium.
Elevated plasma angiotensin II levels are responsible for the elevated aldosterone levels present during the luteal phase of the menstrual cycle
Angiotensin IV is believed to help mediate vaso-constriction, but the causes of this effect is widely unknown.
What is dipsogen? Dipsogen is a medical term referring to an increased thirst sensation.