BIOCHEMICAL EFFECTS OF LOSARTAN, A NONPEPTIDE ANGIOTENSIN-II RECEPTORANTAGONIST, ON THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM IN HYPERTENSIVE PATIENTS

We investigated the effects of angiotensin II (Ang II) type 1 receptor blockade with losartan on the renin-angiotensin-aldosterone system in hypertensive patients (supine diastolic blood pressure, 95 to 110 mm Hg). Qualifying patients (n=51) were allocated to placebo, 25 or 100 m g losartan, or 20 mg enalapril. Blood pressure, plasma drug concentrat ions, and renin-angiotensin-aldosterone system mediators were measured on 4 inpatient days: end of placebo run-in, after first dose, and 2 a nd 6 weeks of treatment. Plasma drug concentrations were similar after the first and last doses of losartan. At 6 weeks, 100 mg losartan and 20 mg enalapril showed comparable antihypertensive activity. Four hou rs after dosing, compared with the run-in day, 100 mg losartan increas ed plasma renin activity 1.7-fold and Ang II 2.5-fold, whereas enalapr il increased plasma renin activity 2.8-fold and decreased Ang II 77%. Both drugs decreased plasma aldosterone concentration. For losartan, p lasma renin activity and Ang II increases were greater at 2 than at 6 weeks. Effects of losartan were dose related. After the last dose of l osartan, plasma renin activity and Ang II changes were similar to plac ebo changes by 36 hours. These results indicate that long-term blockad e of the feedback Ang II receptor in hypertensive patients produces mo dest increases of plasma renin activity and Ang II that do not appear to affect the antihypertensive response to the antagonist.