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This pathway depicts a simplified representation of the pharmacodynamics of the ace inhibitor class of
drugs on candidate genes in the renin-angiotensin-aldosterone pathway (RAAS). Ace inhibitors target the ace
gene product, angiotensin converting enzyme, resulting in downstream reduction of angiotensin, and decreased
aldosterone secretion. The decrease in aldosterone decreases sodium and water resorption in the kidney and
decreases potassium excretion. Through their action on the bradykinin pathway they also increase production
of nitric oxide and induce vasodilation.
As many as 65 million Americans have high blood pressure [American Heart Association]. Hypertension increases
the risk of stroke and heart attack and is a cause of death of over 250,000 Americans per year [American
Heart Association] Ace inhibitors are standard therapy for hypertension and are often given in combination
with other blood pressure lowering medications such as thiazide diuretics for patients at increased risk
[NHLBI]. Angiotensin receptor blocking drugs (ARBs) such as losartan, irbesartan, and candesartan, also
act on the RAAS pathway.
There is considerable inter-individual variation in response to antihypertensive treatments. Pharmacogenomics
offers the potential to improve therapy and achieve better blood pressure control in hypertensive patients.
Much of the pharmacogenomic study of antihypertensives has focused of genes in the RAAS pathway including
angiotensinogen (AGT), angiotensin converting enzyme (ACE), and the angiotensin type I receptor (AGTR1),
with the insertion/deletion (I/D) polymorphism in ACE being the most commonly studied variant. These
polymorphisms have been shown to influence the pharmacodynamic response to ace inhibitors (AGT, ACE, and
AGTR1), ARBs (ACE) and thiazide diuretics (NOS3 and ACE).
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| C. F. Thorn |
| December 3, 2003 |
| October 15, 2007 |
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