THE ADVANTAGES OF ANGIOTENSIN-II ANTAGONISM

New approaches to renin-angiotensin blockade: The successful use of angiotensin converting enzyme (ACE) inhibitors in the treatment of hypertension and congestive heart failure has generated a great deal of research interest in developing new pharmacological approaches to block the renin-angiotensin system. In recent years, several new non-peptide angiotensin II antagonists have been synthesized and some of them are available for experimental and/or clinical investigations. Now that experience with the antagonist losartan is accumulating, it is important to compare the effects, the efficacy and the side effects of this agent with those of ACE inhibitors. Effects of losartan compared with ACE inhibitors: So far, ACE inhibitors and the angiotensin II antagonist losartan appear to have similar systemic and regional hemodynamic effects. The impact of ACE inhibition and angiotensin blockade on the various components of the renin-angiotensin system is also comparable except for a marked increase in plasma angiotensin II levels during angiotensin II blockade. This increase in circulating angiotensin II might theoretically lead to an excessive stimulation of the AT(2) receptor subtype, but since the function of this receptor is not known it is impossible to evaluate the implications of this reactive rise. Renal effects of losartan: The renal effects of angiotensin II antagonists are also very similar to those of ACE inhibitors. However, a marked increase in uric acid excretion has been observed with the administration of losartan. This uricosuric effect of losartan might represent a clinical advantage unless a state of urinary supersaturation of undissociated uric acid is achieved. Preliminary results obtained in water-loaded subjects suggest that this is not the case, but additional information from normohydrated subjects or patients is needed to evaluate the risk of acute uric acid nephropathy under losartan therapy. Losartan versus enalapril in clinical studies: Finally, two clinical studies have now shown that the antihypertensive efficacy of losartan is comparable to that of enalapril. Moreover, preliminary results suggest that in contrast to ACE inhibitors, losartan does not cause a cough. Thus, the angiotensin II antagonist losartan seems to compare favorably with ACE inhibitors. Accordingly, it is not only an interesting new antagonist that can be used to assess the function of the renin-angiotensin system in sustaining blood pressure and peripheral vascular resistance, but is likely to become a useful agent for the treatment of hypertensive patients.