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The Manipulation the Renin-Angiotensin System in the Treatment of Cardiovascular Disease
Natalie Hogg
Introduction
Activation of the renin-angiotensin system is an important factor in the pathogenesis of cardiovascular disease, therefore manipulating this system is an important step in the treatment of cardiovascular diseases. There are various points at which this system can be targeted and to understand this we must first look at how the system works and why it is activated in heart failure.
The renin-angiotensin system acts along with the sympathetic nervous system and once activated cause the secretion of aldosterone from the adrenal cortex, controls sodium excretion, fluid volume and vascular tone. ... The kidney, via renal baroreceptors, detects a decrease in perfusion and activates the system in order to compensate for this. The system acts to increase blood flow to the kidney by increasing blood volume. The response is begun by secretion of renin by the juxtaglomerular apparatus of the kidney. Renin is a proteolytic enzyme which then acts on angiotensinogen (produced in the liver), this forms a small peptide called Angiotensin I. This peptide is then cleaved again by Angiotensin-Converting Enzyme (ACE), a membrane bound enzyme found on the surface of endothelial cells that are found abundantly in the lung. This new peptide is called Angiotensin II, which is a potent vasoconstrictor, along with having many other actions (Diagram 1). ... Renin-Angiotensin System (Klabunde, 2004])
In cardiovascular disease however, activation of this system causes further deterioration in cardiac performance. ... The body registers this as a loss in circulatory volume and therefore reacts to increase this volume by activating RAS and the sympathetic system. ...
Decrease in Cardiac Output
Increased renin production in kidney
Angiotensinogen Angiotensin I
ACE
Angiotensin II
Increase in Increased thirst and Increase in
Aldosterone increased production arterial constriction
of ADH
Salt and water Salt and water Increase in
retention afterload
Oedema Oedema
Figure 2. The Renin-Angiotensin System in Cardiac Failure [Prosser, 2000]
This subsequent increase in volume forces the heart to stretch so it can contract with more force in order to pump out the extra fluid. ... Manipulation of RAS therefore is important in treating cardiovascular disease. The main drugs that are used today which target RAS are ACE Inhibitors and Angiotensin II Receptor Antagonists.
Approximate Word count = 1803
Approximate Pages = 7.2
(250 words per page double spaced)
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