The renin-angiotensin-aldosterone system (RAAS), or renin-angiotensin-system (RAS) is a regulator of blood pressure and cardiovascular function. Dysregulated RAAS is implicated in high blood pressure, cardiovascular and kidney conditions, and medications targeting RAAS can improve these conditions.To get more news about
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What is the renin-angiotensin-aldosterone system (RAAS)?
The RAAS is a complex multi-organ endocrine (hormone) system involved in the regulation of blood pressure by balancing fluid and electrolyte levels, as well as regulating vascular resistance & tone. RAAS regulates sodium and water absorption in the kidney thus directly having an impact on systemic blood pressure.
Typically, RAAS is activated when there is a drop in blood pressure (reduced blood volume) to increase water and electrolyte reabsorption in the kidney; which compensates for the drop in blood volume, thus increasing blood pressure.
Renin
Juxtaglomerular cells in the kidney are abundant in an inactive precursor protein called prorenin which is constantly secreted. Decreased blood pressure activates juxtaglomerular cells, which leads to prorenin being cleaved into its active form – renin, which is then secreted into the bloodstream.
Angiotensin
Renin acts on angiotensin (continuously produced by the liver) to cleave a 10 amino acid peptide from the N-terminus to form angiotensin I (inactive). Angiotensin-converting-enzyme (ACE) further cleaves angiotensin I to form angiotensin II – which is the primary active peptide of RAAS. ACE is primarily found in vascular endothelia of the lungs and the kidneys.
Angiotensin II binds to angiotensin type I A (AT1AR) or B (AT1BR), as well as type II (AT2R) receptors. Angiotensin II is a potent vasoconstrictor, which leads to increased blood pressure. Normally, if blood pressure is too high, atrial natriuretic peptide (ANP) – secreted by cardiac muscle cells – leads to reductions in blood volume, leading to reduced blood pressure.
Angiotensin II binding to AT1R can result in a cascade of inflammation, constriction, and the promotion of atherosclerosis. Furthermore, these events can also lead to insulin resistance and thrombosis, whereas binding to AT2R has opposing effects: vasodilation reduced platelet aggregation and enhanced insulin activity.
Angiotensin II also acts on the brain where it can bind to the hypothalamus to stimulate thirst to increase water intake. By acting on the pituitary gland, angiotensin II also stimulates the secretion of vasopressin; also known as antidiuretic hormone, which increases water retention in the kidneys by adding water channels (aquaporin) to the collecting duct.
Dysfunctional RAAS
Primary pathologies of impaired RAAS include chronic hypertension, kidney, and cardiac failure. Abnormally active RAAS leads to chronic hypertension and thus the high blood pressure needs to be counterbalanced.
ACE inhibitors are commonly used drugs in the treatment and management of hypertension and heart failure. ACE inhibition prevents the conversion of angiotensin I to angiotensin II, thus keeping angiotensin inactive.
Angiotensin II binding to AT1R can also induce cardiac dysfunction including hypertrophy, arrhythmia, and ventricle function failure. Excessive angiotensin II can also lead to large inflammatory changes such as cytokine-induced organ damage in addition to increased membrane permeability and epithelial cell apoptosis.
As angiotensin II is a vasoconstrictor, alleviation causes vasodilation thus reducing systemic blood pressure levels. ACE inhibitors also lead to the increased production of bradykinin – which is a vasodilator. Other drugs include angiotensin receptor blockers (ARBs) – which block the binding of angiotensin II to ATRs. ACE inhibitors and ARBs are also effective drugs in the management of heart failure and complications of diabetes.
In the kidney, renal arterial stenosis leads to decreased blood volume entering the kidneys; consequently, juxtaglomerular cells sense a decreased blood volume and RAAS is activated. This, negatively, enhances blood pressure further which is inappropriate to the systemic circulation as well as increasing arterial tone. Thus, ACE inhibitors and ARBs can also be used in patients with renal arterial stenosis to limit the inappropriate activation of RAAS.
