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 im portant information, as long as the compound has a specific mechanism of action which can be evaluated in healthy subjects as well as in pat ients. The purpose of the present paper is to review the renal effects of new specific angiotensin II receptor antagonists observed in normo tensive subjects and to compare them to those of angiotensin-convertin g enzyme (ACE) inhibitors. Blockade of the renin-angiotensin system wi th ACE inhibitors and angiotensin II antagonists induces an expected i ncrease in plasma renin activity and plasma angiotensin I levels. Plas ma angiotensin II levels decrease with ACE inhibitors, whereas they in crease with angiotensin II receptor blockade. So far, the expected dec rease in plasma aldosterone levels has been difficult to demonstrate w ith most angiotensin II antagonists. In normotensive subjects, ACE inh ibitors, as well as angiotensin II antagonists, cause no change in glo merular filtration rate and either no modification or an increase in r enal blood flow. Both approaches to block the renin-angiotensin system are natriuretic, and the natriuresis is more pronounced in salt-deple ted subjects. Finally, in contrast to ACE inhibitors and other angiote nsin II receptor antagonist, losartan markedly increases uric acid exc retion and lowers plasma uric acid levels. This unique property of los artan is due to a direct interference of losartan with the uric acid t ransport system in the proximal tubule. The data obtained in normal su bjects therefore suggest that ACE inhibitors and angiotensin II recept or antagonists have comparable renal properties. Whether this is also true in hypertensive patients and in patients with proteinuria and chr onic renal failure remains to be demonstrated.