Renin Angiotensin System
The juxtaglomerular apparatus is made up of specialized arteriolar smooth muscle cells that are sited on the afferent glomerular arteriole as it enters the glomerulus. These cells secrete renin, which converts angiotensinogen in blood to angiotensin I. Renin release is controlled by:
- pressure changes in the afferent arteriole
- sympathetic tone
- chloride and osmotic concentration in the distal tubule via the macula densa.
- local prostaglandin release.
Angiotensin II is generated from angiotensin I by angiotensin-converting enzyme (ACE). Angiotensin II is both a vasoconstrictor and the most important stimulus for the release of aldosterone by the adrenal cortex. It also modifies intrarenal blood flow.
The renin-angiotensin-aldosterone axis: biochemistry and actions
Angiotensinogen, an alpha 2 -globulin of hepatic origin, circulates in plasma. The enzyme, renin, is secreted by the kidney in response to decreased renal perfusion pressure or flow; it cleaves the decapeptide angiotensin I from angiotensinogen. Angiotensin I is inactive but is further cleaved by angiotensin-converting enzyme into the active peptide, angiotensin II, which has two major actions:
- it causes rapid, powerful vasoconstriction
- it stimulates the adrenal zona glomerulosa to increase aldosterone production.
The vasoconstrictor action of angiotensin II occurs in seconds to minutes, while aldosterone causes sodium retention and urinary potassium loss, leading to increased total body sodium and BP over hours to days.
As BP increases and sodium is retained, the stimuli to renin secretion are reduced. Dietary sodium excess also suppresses renin secretion, whereas sodium deprivation or urinary sodium loss will increase it.
The renin-angiotensin system can be blocked at several points with renin inhibitors, angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists (A-IIRA). The latter two are useful agents in treatment of hypertension and heart failure though have differences in action: ACEIs also block kinin production while A-IIRAs are specific for the AT-II receptor.
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