Renal effects of angiotensin II receptor blockade and angiotensin-converting enzyme inhibition in healthy subjects.

The evaluation of a new drug in normotensive volunteers can provide important information, as long as the compound has a specific mechanism of action which can be evaluated in healthy subjects as well as in patients. The purpose of the present paper is to review the renal effects of new specific angiotensin II receptor antagonists observed in normotensive subjects and to compare them to those of angiotensin-converting enzyme (ACE) inhibitors. Blockade of the renin-angiotensin system with ACE inhibitors and angiotensin II antagonists induces an expected increase in plasma renin activity and plasma angiotensin I levels. Plasma angiotensin II levels decrease with ACE inhibitors, whereas they increase with angiotensin II receptor blockade. So far, the expected decrease in plasma aldosterone levels has been difficult to demonstrate with most angiotensin II antagonists. In normotensive subjects, ACE inhibitors, as well as angiotensin II antagonists, cause no change in glomerular filtration rate and either no modification or an increase in renal blood flow. Both approaches to block the renin-angiotensin system are natriuretic, and the natriuresis is more pronounced in salt-depleted subjects. Finally, in contrast to ACE inhibitors and other angiotensin II receptor antagonist, losartan markedly increases uric acid excretion and lowers plasma uric acid levels. This unique property of losartan is due to a direct interference of losartan with the uric acid transport system in the proximal tubule. The data obtained in normal subjects therefore suggest that ACE inhibitors and angiotensin II receptor antagonists have comparable renal properties. Whether this is also true in hypertensive patients and in patients with proteinuria and chronic renal failure remains to be demonstrated.