HEMODYNAMIC AND HUMORAL EFFECTS OF THE ANGIOTENSIN-II ANTAGONIST LOSARTAN IN ESSENTIAL-HYPERTENSION

Losartan (DuP 753) is a novel orally active angiotensin II antagonist that lowers blood pressure. The present study evaluates the hemodynami c and humoral effects of losartan in essential hypertension. Fifteen p atients (12 men, 3 women; mean age, 46 +/- 2 years; range, 33 to 64 ye ars) with a diastolic blood pressure (DBP) between 95 and 115 mm Hg af ter 2 weeks of placebo participated in the study. Initially the patien ts were treated with losartan (50 mg) once daily for 1 month. Then, if the trough DBP was greater than or equal to 93 mm Hg, hydrochlorothia zide (HCTZ), 6.25 to 12.5 mg daily, and nifedipine, 30 to 60 mg daily, were added as needed. Ten patients completed 12 months of treatment. Trough blood pressure, heart rate, plasma creatinine, potassium, uric acid, cholesterol, renin activity (PRA), aldosterone, and norepinephri ne were measured at baseline and after 1 and 12 months of treatment. L osartan lowered mean arterial pressure significantly from 119 +/- 2 mm Hg at baseline to 113 +/- 2 mm Hg (P <.05) after 1 month of treatment . Coadministration of HCTZ and nifedipine further decreased the mean a rterial pressure to 103 +/- 2 mm Hg after 12 months of treatment. Plas ma levels of creatinine, potassium, uric acid, cholesterol, and norepi nephrine remained unchanged. PRA increased and plasma aldosterone decr eased significantly (P <.05). The decrease in mean arterial pressure w as related to baseline PRA (r = 0.53, P <.05) and to the change in PRA (r = 0.52, P <.05). Our results indicate that losartan can be used sa fely as an antihypertensive agent, and that its efficacy is more promi nent in patients with high renin hypertension.