Effects of candesartan on the proteinuria of chronic glomerulonephritis

Abstract

Angiotensin I-converting enzyme (ACE) inhibitors are commonly used for the treatment of hypertension, progressive chronic renal disease, diabetic nephropathy, and congestive heart failure. Because angiotensin II acts through membrane bound type 1 (AT₁) and type 2 (AT₂) receptors, ACE inhibitors and angiotensin II-receptor antagonists have distinct effects. ACE inhibitors inhibit production of angiotensin II thus suppressing the action of angiotensin II on both AT₁ and AT₂. In contrast, the effect of AT₁-receptor antagonists is to selectively block the activation of the AT₁ receptor. This AT₁-receptor blockade leaves the AT₂ receptors unopposed to elevated levels of endogenous angiotensin II. Thus, there may be an advantage of AT₁-receptor blockade over ACE inhibition in the management of a variety of chronic vascular diseases, including chronic glomerulonephritis and other glomerular diseases. In a clinical trial candesartan, an AT₁-receptor antagonist, effectively lowered urinary protein excretion in patients with chronic glomerular nephritis. Evidence indicates that functionally active AT₁ receptors, as well as AT₂ receptors, are present in both afferent and efferent arteriole of the glomerulus, and that angiotensin II induces afferent and efferent arteriolar dilatation via AT₂ receptors.