PHARMACOLOGICAL DEMONSTRATION OF THE ADDITIVE EFFECTS OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITION AND ANGIOTENSIN-II ANTAGONISM IN SODIUM-DEPLETED HEALTHY-SUBJECTS

A blockade of the hemodynamic and tissue effects of angiotensin II (An g II) more complete than that presently achieved with usual daily dose s of angiotensin converting enzyme (ACE) inhibitors or type 1 Ang II r eceptor antagonists has potential advantages and risks. Therefore, it is worthwhile to investigate the biological and the hemodynamic effect s of the simultaneous blockade of the renin-angiotensin system (RAS) a t the two sites where it can be currently achieved, ACE and type 1 Ang II receptors. To investigate this issue, 2 double-blind randomized cr ossover studies were performed in a model of mild sodium depletion in normotensive volunteers. They ingested single oral doses of captopril 50 mg, losartan 50 mg, their combination or matched placebos, and in a second study, single oral doses of enalapril 10 mg, enalapril 20 mg a nd the combination of losartan 50 mg with enalapril 10 mg. The combina tion captopril 50 mg and losartan 50 mg had additive effects on blood pressure fall and renin release in sodium-depleted normotensive subjec ts. When compared to enalapril 10 mg and the doubling of its dose, the combination of losartan 50 mg and enalapril 10 mg significantly incre ased both the area under the time curve of mean blood pressure fall an d plasma active renin levels. It did not further decrease plasma aldos terone levels. The conclusion is that a more complete blockade of the RAS can be achieved by concomitant administration of an type 1 Ang II receptor antagonist and an ACE inhibitor.