Effects of losartan on the renin-angiotensin-aldosterone axis in essential hypertension

Twelve essential hypertensive patients were entered into a prospective study assessing the effect of losartan, a non-peptide specific angiotensin II receptor antagonist, on blood pressure, the renin-angiotensin-aldosterone axis and renal function. Specifically monitored prior to and following 12 weeks of therapy at 6 (peak) and 24 (trough) h after dosing, were blood pressure, plasma renin activity (PRA), plasma aldosterone, and plasma angiotensin II (Ang II), creatinine clearance and urinary albumin excretion (UAE). In this small sample of hypertensive patients, losartan monotherapy and losartan-hydrochlorothiazide (HCTZ) combination therapy were associated with modest reductions in systolic, diastolic and mean arterial BPs; significant changes were observed only at the peak dosing interval. Losartan, given as either monotherapy or combination therapy, was associated with an increase in the 'trough' values of PRA; significant changes in the 'trough' values of plasma Ang II and plasma aldosterone were not observed. In contrast, PRA and plasma Ang II were stimulated, and plasma aldosterone was depressed, 6 h after dosing. There were significant negative correlations between both PRA and plasma Ang II reactivity (difference between PRA or plasma Ang II values obtained 6 h after placebo dosing and 6 h after drug dosing) and the change in systolic, diastolic and mean arterial BPs. Of interest, losartan/HCTZ combination therapy was associated with a decrease in the creatinine clearance; UAE was not significantly altered. Losartan appears to be an effective anti-hypertensive agent in patients with mild to moderate hypertension. Its peak BP effect appears to be at the dosing interval corresponding to pharmacological blockade of angiotensin II receptors. Furthermore, this anti-hypertensive agent may be more efficacious in patients with a reactive renin-angiotensin system.