Renin-Angiotensin-Aldosterone System (RAAS)

Effects

The RAAS is activated in the presence of low blood pressure, decreased blood volume, hyponatremia, and sympathetic activation. Main actions: mediated via angiotensin II:

• Vasoconstriction
• Blood pressure increase
• Release of catecholamines
• Hypertrophy at the heart

Mediated via aldosterone:

• Water and sodium ions are retained
• Potassium ions and protons are eliminated

Overview of the RAAS

Components of the RAAS

• An aspartyl protease that catalyzes the cleavage of angiotensinogen to angiotensin I. Renin is produced by juxtaglomerular cells in the kidneys under regulation of the sympathetic nervous system (β₁). Renin is released during hypovolemia, low blood pressure, hyponatremia, and sympathetic stimulation.

• A dipeptidyl carboxypeptidase that converts angiotensin I to angiotensin II. ACE is mainly localized on the surface of endothelial cells facing the lumen of blood vessels. The lung is an important organ for the formation of angiotensin II.

• A decapeptide and the inactive peptide substrate for angiotensin I.

• An octapeptide that, among other things, constricts vessels, increases blood pressure, increases secretion of catecholamines, vasopressin, and ACTH, and promotes the synthesis of aldosterone, and is a growth stimulus for cardiac and vascular smooth muscle.

• Aldosterone is a mineralocorticoid produced in the zona glomerulosa, the outermost layer of the adrenal cortex. It increases at the kidney the reabsorption of sodium ions and water and promotes the excretion of potassium ions and protons into the urine.

• Is a degradation product of angiotenin II.

Drug inhibition of the RAAS

Indications: Hypertension, heart failure, oedema, renal disease Renin inhibitors inhibit renin and prevent angiotensin II formation:

• Aliskiren

ACE inhibitors inhibit ACE and the formation of angiotensin II from angiotensin I:

• Benazepril, captopril, cilazapril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, trandolapril, zofenopril.

Sartanes abolish the effects of angiotensin II at the AT₁ receptor:

• Losartan, valsartan, irbesartan, candesartan, eprosartan, olmesartan, telmisartan.

Aldosterone antagonists abolish the effects of aldosterone:

• Spironolactone, Canrenone, Eplerenone.