Hypotensive Effect of Losartan, a Nonpeptide Angiotensin II Receptor Antagonist, in Essential Hypertension

Abstract

We examined the chronic effects of losartan (DuP 753), a novel orally active angiotensin II receptor antagonist, on blood pressure and renal function in eight hospitalized patients with essential hypertension. After a control period of 1 week, losartan was administered orally once a day for 2 to 4 weeks in increasing doses of 12.5, 25, 50, and 100 mg, until blood pressure in the supine position decreased more than 20 mm Hg (systolic) and 10 mm Hg (diastolic) (or 13 mm Hg in mean blood pressure). The average dose of losartan was 59.4 +/- 43.7 (mean +/- SD) mg/day. Systolic, diastolic, and mean blood pressures, according to 24 h monitoring, fell significantly, from 151.9 +/- 6.8 to 137.2 +/- 7.9 mm Hg, from 90.6 +/- 3.7 to 81.0 +/- 3.7 mm Hg, and from 111.1 +/- 4.6 to 99.7 +/- 5.0 mm Hg, respectively (mean +/- SE, P < .01 for each), with no change in circadian rhythm or variability of blood pressure. Reduction in blood pressure was slightly greater during daytime than during sleep time. Unlike peptide angiotensin II antagonists, losartan did not exert pressor action. No significant alterations were observed in body weight, serum electrolytes, creatinine clearance, urine volume, or urinary excretion of sodium. Losartan significantly lowered serum uric acid concentration from 5.5 +/- 0.4 to 4.8 +/- 0.3 mg/dL (P < .05). Urinary excretion of uric acid increased significantly from 498.9 +/- 64.4 to 540.6 +/- 66.6 mg/day (P < .05). Plasma renin activity rose significantly but plasma aldosterone concentration did not change with the losartan treatment. These results suggest that losartan has a long-acting hypotensive effect with a hypouricemic action in essential hypertension.

Comparative effects of chronic ACE inhibition and AT1 receptor blocked losartan on cardiac hypertrophy and renal function in hypertensive patients

“…3 Clinical trials have demonstrated that losartan potassium given alone lowers blood pressure (BP) and is well tolerated in longterm trials in patients with essential hypertension. 4 Despite the efficacy of losartan potassium or other monotherapy agents such as hydrochlorothiazide (HCTZ), some patients with more resistant forms of hypertension may require concomitant antihypertensive therapy to control their BP. 5 The purpose of this 3-year trial was to assess the long-term effects of ACE inhibitors (enalapril) vs selective AT1 receptor blockade (losartan) on reactive cardiac hypertrophy and on renal function in patients with mild to moderate essential hypertension.…”

Clinical Efficacy of a New Angiotensin II Type 1 Receptor Blocker, Pratosartan, in Hypertensive Patients

“…For example, telmisartan has been reported to be beneficial for glucose and lipid metabolism (13,14), and losartan to be beneficial for uric acid reduction (6)(7)(8)(9)(10). The present study demonstrated that PRT may be of benefit in cholesterol and uric acid metabolism, although we can not exclude the possibility that the reduction of uric acid and cholesterol may be affected by diet, because we did not control diet during the study period.…”

Efficacy and Safety of Long-Term Losartan Therapy Demonstrated by a Prospective Observational Study in Japanese Patients with Hypertension: The Japan Hypertension Evaluation with Angiotensin II Antagonist Losartan Therapy (J-HEALTH) Study

“…Losartan has been reported to decrease the serum uric acid level in normal volunteers (32) and in hypertensive patients (33). Losartan inhibits the uric acid transporter (URAT1) and thus decreases the serum uric acid level, while other ARBs only inhibit URAT1 weakly (34,35).…”