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Diabetic nephropathy is the main cause of end stage renal disease both in the USA and in Europe. In addition, the development of diabetic nephropathy greatly increases the cardiovascular risk in these patients. Studies performed with angiotensin converting enzyme (ACE) inhibitors have shown that blockade of the actions of angiotensin II (AII) is the treatment of choice for diabetic patients who have developed microalbuminuria.
ACE inhibitors and AT1 inhibitors
Studies demonstrating the positive effects of ACE inhibitors have all shown that these drugs are able to decrease the risk of nephropathy, once chronic failure is present, by 50%. It is hoped that a new way of blocking the effects of angiotensin II could decrease the risk even further. Interest has particularly focused on the emerging role of the angiotensin II receptor antagonists.
MECHANISM OF ACTION
Distribution of the ACE and angiotensin II type I (AT1) receptor in the kidney is very different. ACE is mostly found in the medulla, while AT1 receptors are present in the inner medulla and the cortex. This contrasting distribution could mean that blockade of each could achieve different renal effects.
With an ACE inhibitor, there is decreased stimulation of the AT1 receptor because less angiotensin II is formed and therefore less is available to bind with the receptor. In contrast, an AT1 antagonist binds to the receptor and occupies the position that angiotensin II would normally have. By impairing the binding of angiotensin II in this way, there is a more complete blockade of the effects of AII (table 1).
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Pharmacological effects of AT1 receptor antagonists and ACE inhibitors
When an AT1 antagonist is administered there is an increase in angiotensin II, which then binds …